Gender, male and female has always been of great interest and present in almost all fiction and films, within different perspectives. Ever since the dawn of time, man has taught ethics, morals, values and existential questions using fictional stories in oral and later in written form. The aim of analyzing the concept of male and female from fiction and film is to reach deeper insight and understanding of human beings with special reference to gender in both individual, group and community perspective. The general aim is to create security in our gender and professional roles. Whole or parts of books and films are used, chosen according to the specific learning outcome. Different aspects are then discussed in lectures, seminars or groups. Aspects include projections, culture and behavior. Students learn to reach a deeper insight and understanding of gender regarding behavior, communication, attitudes, values, culture and ethnicity. Peeling off the illusion of male and female created by our social structure, and making our values and prejudices conscious, we might discern the eternally human, the inner core of being human, regardless of sex. Fiction and film make conscious behavior, communication and gender, and merge cognition and emotions. This way of teaching may lead to better treatment of patients by health care personnel

Cigarette smoking is a leading cause of cardiovascular disease. The cardiovascular effects of smoking are probably multifactorial, including effects on platelets. Previous reports investigating the effects of nicotine and tobacco on platelet function are inconsistent.

The present study investigated in vitro effects of nicotine, its major metabolites, tobacco extracts and extract of tobacco-free snuff on human platelets.

None of the metabolites cotinine, cotinine-N-oxide, nicotine-1′-N-oxide or trans-3′-hydroxycotinine (0.1–10 μM) affected platelet aggregation or P-selectin expression. Nicotine (10 μM) weakly increased platelet aggregation, whereas trans-3′-hydroxycotinine (0.1 μM) and nicotine-1′-N-oxide (1–10 μM) weakly inhibited adhesion to fibrinogen. To elucidate the influence of other tobacco compounds, we investigated the impact of moist tobacco and smoke extracts on platelet function. Filtered extracts of oral snuff, cigarette smoke and tobacco free snuff inhibited platelet adhesion concentration-dependently. The inhibitory effects of tobacco extracts on platelet adhesion were independent of nicotine content and the nitric-oxide-pathway and not mediated through a platelet-nicotine-receptor.

Taken together, tobacco extracts inhibit platelet activation during short-term in vitro challenge. As only limited effects of nicotine and nicotine metabolites were seen, the tobacco-induced platelet inhibition are likely induced by other compounds present in tobacco and tobacco free snuff.

Aim: This study aimed to explore the link between angiotensin-converting enzyme (ACE), and left ventricular (LV) function and central hemodynamics.

Methods and Results: The study population consisted of 672 subjects (322 men and 350 women) aged 69-87 years. LV function was evaluated semi-quantitatively by visual estimation using echocardiography. Central aortic blood pressure, aortic augmentation and pulse pressure amplification were determined in a sub-group of 422 subjects by the use of the SphygmoCor system. ACE genotype was determined by PCR and circulating ACE levels were analysed using enzyme-linked immunosorbent assay (ELISA).

LV dysfunction was associated with higher levels of circulating ACE compared to subjects with normal LV function (p=0.007). This association remained after adjustment for factors previously shown to affect circulating ACE (ACE-genotype, age, diabetes and smoking) (p=0.036). There was a significant association between ACE level and degree of LV dysfunction (p=0.019). However, there was no association of ACE genotype or circulating ACE with central aortic blood pressure, aortic augmentation or pulse pressure amplification.

Conclusion: Subjects with LV dysfunction have higher levels of circulating ACE compared to subjects with normal LV function. ACE might play a role in the pathogenesis of LV dysfunction and our data indicates a direct effect on the heart rather than affecting central blood pressure.

Evidence suggests that cocoa from the bean of Theobroma cacao L. has beneficial effects on cardiovascular disease. The aim of this study was to investigate if cocoa extract and dark chocolate influence angiotensin-converting enzyme (ACE) and nitric oxide (NO) in human endothelial cells (in vitro) and in healthy volunteers (in vivo). ACE activity was analyzed with a commercial radioenzymatic assay and measured in human endothelial cells from umbilical veins (HUVEC) after 10 minutes of incubation with cocoa extract. NO was measured after 24 hours of incubation. ACE activity and NO were measured at baseline and after 30, 60, and 180 minutes in 16 healthy volunteers after a single intake of 75 g of dark chocolate containing 72% cocoa. Significant inhibition of ACE activity (P < 0.01) and significant increase of NO (P < 0.001) were seen in HUVEC. In the study subjects, a significant inhibition of ACE activity (mean 18%) 3 hours after intake of dark chocolate was seen, but no significant change in NO was seen. According to ACE genotype, significant inhibition of ACE activity was seen after 3 hours in individuals with genotype insertion/insertion and deletion/deletion (mean 21% and 28%, respectively). Data suggest that intake of dark chocolate containing high amount of cocoa inhibits ACE activity in vitro and in vivo.

BACKGROUND The functional plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism has previously been associated with hypertension. In recent years, central blood pressure, rather than brachial has been argued a better measure of cardiovascular damage and clinical outcome. The aim of this study was to investigate the possible influence of the 4G/5G polymorphism on central arterial blood pressure in a cohort of elderly individuals. METHODS We studied 410 individuals, 216 men and 194 women, aged 70-88. Central pressures and pulse waveforms were calculated from the radial artery pressure waveform by the use of the SphygmoCor system and a generalized transfer function. Brachial pressure was recorded using oscillometric technique (Dinamap, Critikon, Tampa, FL). PAI-1 antigen was determined in plasma. RESULTS The results showed that central pressures were higher in women carrying the PAI-1 4G/4G genotype compared to female carriers of the 5G/5G genotype, (P = 0.025, P = 0.002, and P = 0.002 for central systolic-, diastolic-, and mean arterial pressure, respectively). The association remained after adjustment for potentially confounding factors related to hypertension. No association of the PAI-1 genotype with blood pressure was found in men. Multiple regression analysis revealed an association between PAI-1 genotype and plasma PAI-1 levels (P = 0.048). CONCLUSIONS Our findings show a gender-specific association of the PAI-1 4G/5G polymorphism with central arterial blood pressure. The genotype effect was independent of other risk factors related to hypertension, suggesting that impaired fibrinolytic potential may play an important role in the development of central hypertension in women.

Objective: A genetic polymorphism in the angiotensin-converting enzyme gene (ACE I/D polymorphism) has been associated with abdominal aortic aneurysm and a link between aortic aneurysm and aortic stiffness has been suggested. The aim of this study was to explore the links between ACE I/D polymorphism, circulating ACE, and abdominal aortic wall integrity as reflected by abdominal aortic wall stiffness.

Material: The study population consisted of 406 subjects (212 men and 194 women) aged 70-88 years.

Methods: The mechanical properties of the abdominal aorta were determined 3-4 cm proximal to the aortic bifurcation using a Wall Track System. ACE-genotype was determined by PCR followed by gel electrophoresis, and circulating ACE level was measured by ELISA.

Results: Men carrying the ACE D allele had lower distensibility coefficient than II carriers (ID/DD 8.09 vs II 10.38, P=0.017). Multiple regression analyses showed additional associations between the ACE D allele and increased stiffness β as well as reduced cross-sectional compliance.

Conclusion: This study showed that men carrying the ACE D allele have stiffer abdominal aortas compared to II carriers. Deranged abdominal aortic stiffness indicates impaired vessel wall integrity, which along with other local predisposing factors, may be of importance in aneurysmal disease.

INTRODUCTION: A polymorphism in the angiotensin-converting enzyme gene (ACE I/D polymorphism) has been associated with increased risk for cardiovascular disease (CVD). This polymorphism affects the level of circulating ACE, but there is great individual variation, even between those with the same genotype. Few previous studies have investigated the link between circulating ACE and cardiovascular risk. The aim of this study was to investigate this association, and to examine the relationship between ACE level, ACE genotype and CVD.

MATERIALS AND METHODS: The study population consisted of 322 men and 350 women aged 69-87. Plasma ACE level was determined using enzyme-linked immunosorbent assay (ELISA), and ACE genotype was analysed using PCR followed by gel electrophoresis.

RESULTS: In men, ACE levels increased with increasing number of cardiovascular risk factors (p = 0.003). There was a significant association in men between increased ACE level and both diabetes (p = 0.007) and smoking (p = 0.037).

CONCLUSIONS: This study shows that cardiovascular risk factors (such as smoking and diabetes) are associated with higher levels of circulating ACE in men. High ACE levels may represent one of the cellular mechanisms involved in producing the vascular damage associated with cardiovascular risk factors.

OBJECTIVE: Tea has been reported to reduce cardiovascular mortality, but the underlying mechanisms are largely unknown. The aim of the current project was to investigate the effect of green tea (Japanese Sencha), black tea (Indian Assam B.O.P.) and Rooibos tea (South Africa) on angiotensin-converting enzyme (ACE) and nitric oxide (NO). DESIGN: Seventeen healthy volunteers received a single oral dose of 400 ml green tea, black tea or Rooibos tea in a randomized, three-phase, crossover study. ACE activity and NO concentration were measured (at 0, 30, 60 and 180 min) in all phases. ACE activity was analysed by means of a commercial radioenzymatic assay. Nitrite was analysed as a marker of NO concentration. In addition, ACE genotype was determined using a PCR method. RESULTS: Oral intake of a single dose of Rooibos tea significantly inhibited ACE activity after 30 min (P < 0.01) and after 60 min (P < 0.05). A significant inhibition of ACE activity was seen with green tea for the ACE II genotype 30 min after intake of the tea (P < 0.05) and for the ACE ID genotype 60 min after intake (P < 0.05). A significant inhibition of ACE activity was also seen with Rooibos tea for the ACE II genotype 60 min after intake (P < 0.05). No significant effect on NO concentration was seen. CONCLUSIONS: These results suggest that green tea and Rooibos tea may have cardiovascular effects through inhibition of ACE activity.

Extract from seeds and bark of horse chestnut (Aesculus hippocastanum L) is used as an herbal medicine against chronic venous insufficiency. The effect and mechanism of action on veins, arteries, and platelets are not fully understood. The aim of this study was to investigate the effects and mechanisms of action of horse chestnut on the contraction of bovine mesenteric veins and arteries, and human platelet aggregation. Contraction studies showed that horse chestnut extract dose-dependently contracted both veins and arteries, with the veins being the most sensitive. Contraction of both veins and arteries were significantly inhibited by the 5-HT(2A) receptor antagonist ketanserin. No effect on contraction was seen with the cyclooxygenase inhibitor indomethacin, the alpha(1) receptor antagonist prazosin or the angiotensin AT(1) receptor antagonist saralasin neither in veins nor arteries. ADP-induced human platelet aggregation was significantly reduced by horse chestnut. A further reduction was seen with the extract in the presence of ketanserin. In conclusion, horse chestnut contraction of both veins and arteries is, at least partly, mediated through 5-HT(2A) receptors. Human platelet aggregation is reduced by horse chestnut. The clinical importance of these findings concerning clinical use, possible adverse effects, and drug interactions remains to be investigated. Copyright (c) 2010 John Wiley & Sons, Ltd.

This is a description of a 7.5 ECTS credits course in drug-pedagogics suitable for pharmacy students. The aim of this course is to provide the students with skills as informants/communicators concerning drugs and use at individual, group and community levels. The course includes advanced studies in drug-pedagogics from psychological, sociological and pharmacological perspective. The examination consists of an individual implementation of oral drug information to a group.

Genome wide association studies have consistently reported associations between a region on chromosome 9p21.3 and a broad range of vascular diseases, such as coronary artery disease (CAD), aortic and intracranial aneurysms and type-2 diabetes (T2D). However, clear associations with intermediate phenotypes have not been described so far. To shed light on a possible influence of this chromosomal region on arterial wall integrity, we analysed associations between single nucleotide polymorphisms (SNPs) and degree of stiffness of the abdominal aorta in elderly individuals.

A total of 400 subjects, 212 men and 188 women, aged 70-88 years were included. Arterial stiffness was examined at the midpoint between the renal arteries and the aortic bifurcation. Two CAD- and aneurysm-associated SNPs (rs10757274 and rs2891168) and one T2D-associated SNP (rs1081161) within the 9p21.3 region were genotyped. Aortic compliance and distensibility coefficients were higher in carriers of the rs10757274G and rs2891168G alleles in men reflecting a decrease in aortic stiffness. Adjustment for age and mean arterial pressure had no effect on these associations. The two SNPs were not associated with intima-media thickness or lumen diameter of the abdominal aorta. There were no associations between the rs10811661 SNP and any measure of aortic stiffness.

Impaired mechanical properties of the arterial wall may explain the association between chromosome 9p21.3 polymorphisms and vascular disease.

This study investigates if the connection between Vaccinium myrtillus and angiotensin-converting enzyme (ACE) might be an explanation of the pharmacological effects on circulation. Cultured endothelial cells from human umbilical veins were incubated with bilberry 25E extract. The main anthocyanidins combined in myrtillin chloride and separately in cyanidin, delphinidin, and malvidin, respectively, were examined concerning their effects on ACE. After 10 min of incubation with bilberry 25E, a significant, dose-dependent inhibition of ACE activity was seen, and after incubation with myrtillin chloride a significant inhibition was seen. No effect was seen with the anthocyanidins. The effect seems to be dependent on this specific mixture of anthocyanins in the bilberry. V. myrtillus may thus have the potential to prevent and protect against cardiovascular diseases.

Tea has been reported to reduce cardiovascular mortality, but the mechanisms behind are largely unknown. The aim of this project was to investigate the effect of green tea (Japanese Sencha), black tea (Indian Assam B.O.P.) and Rooibos on angiotensin-converting enzyme and nitric oxide. Seventeen healthy volunteers received a single oral dose of either 400 ml green tea, black tea or Rooibos tea in a randomized three-phase cross over study. ACE activity and NO concentration were measured (at 0, 30, 60 and 180 minutes) in all phases. ACE activity was analysed with a commercial radioenzymatic assay. Nitrite was analysed as a marker of NO concentration. In addition ACE genotype was determined using a PCR method. Oral intake of a single dose of Rooibos significantly inhibited ACE activity, p<0.01 after 30 min and p<0.05 after 60 min. A significant inhibition of ACE activity was seen with green tea for the ACE genotype II (p<0.05), 30 minutes after intake of the tea and for the ACE genotype ID (p<0.05), 60 minutes after intake. A significant inhibition of ACE activity was also seen with Rooibos for the ACE genotype II (p<0.05), 60 minutes after intake. No significant effect on NO concentration was seen.

Abstract

Extract from seeds and bark of the horse chestnut tree Aesculushippocastanum L. (Hippocastanaceae) is today used as herbal medicine in Europe against chronic venous insufficiency (CVI; i.e. varicose veins accompanied with pain, oedema, pruritus and a sense of heaviness). Administration is oral (e.g. Venastat®, Venokan®) or topical (Reparil). Recommended oral dose is 50 mg aescin twice a day. The standardized extract mostly used is D.H.E. (Bernett, Milan, Italy; standardized for 16-22% triterpene saponins). Prior to treatment, other diseases (e.g. venous thrombosis) should be excluded. Oral administration with horse chestnut capsules has in clinical studies been shown to be more effective than placebo and as effective as compression stockings in CVI. The main constituents of horse chestnut are triterpene saponins (i.e. aescin), flavonoids (e.g. quercetin, kaempherol, epicatechin, proanthocyanidin A anthocyanins) and coumarins (e.g. esculin, esculetin). Aescin (also called escin) is actually a mixture of more than 30 different triterpene saponin glycosides of which the main component is suggested to be the active component and is the major content of pharmaceutical products. Mainly three effects of horse chestnut extract on CVI can be identified: anti-oedomatous, anti-inflammatory and venotonic. The anti-inflammatory effect includes free oxygen radical scavenging and decreased vascular permeability. Also, inhibition of elastase, collagenase 2,b-aescin (C55H86O24). b-aescin is and hyaluronidase in the vascular wall has been observed. Adverse effects are few and include gastrointestinal symptoms, nausea, headache, dizziness and allergy. Possible contraindications and drug interactions have not been studied.

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Oxidized low-density lipoprotein (LDL) diminishes NO production from activated macrophages. The interaction between LDL and inactivated macrophages is neglected and controversial. This study examines the effect of LDL, 7-oxysterols and iron compounds on NO production in unstimulated J774 macrophages. J774 cells and human umbilical vein endothelial cells (HUVEC) were either incubated for 24 h with native LDL (LDL) or ultraviolet (UV)-oxidized LDL (UVoxLDL), in the absence or presence of an inducible nitric oxide synthase (iNOS)- or an endothelial constitutive nitric oxide synthase (eNOS)-inhibitor. J774 cells were also incubated with lipopolysaccharide (LPS), in the absence or presence of an iNOS- or an eNOS-inhibitor. Nitrite was analysed as a marker of NO production. The mRNA levels of iNOS were evaluated by reverse transcriptase polymerase chain reaction. LDL and UVoxLDL significantly increased NO production from unstimulated J774 macrophages. This increase in NO was accompanied by enhanced expression of iNOS mRNA, and was inhibited by the iNOS inhibitor. Furthermore, NO production was elevated and angiotensin-converting enzyme (ACE) activity was reduced in HUVEC following the exposure to LDL and UVoxLDL. In conclusion, LDL may serve as an important inflammatory activator of macrophages and HUVEC, inducing inducible nitric oxide production but diminishing ACE. After its oxidation, this function of LDL may be further enhanced and may contribute to the regulation and progression of atheroma formation.

This book contains 27 research and review papers that cover the recent progress in medicinal plant research, e.g. therapeutic efficacy of Bidens pilosa var. radiata and Galinsoga parviflora in experimentally induced diarrhoea in mice, new antioxidant flavonoids from Atriplex lentiformis and analysis of polyphenols with potential antioxidant properties in wines from Croatia.

Up to 138 more results found for "phytopharmacology AND therapeutic values v''"

Flavonoids, carotenoids and tocopherols are antioxidants with alleged positive effect on the cardiovascular system. To investigate other possible pharmacological mechanisms, we examined common substances from these groups and others derived from the same biosynthesis pathway concerning their effect on angiotensin-converting enzyme (ACE) activity in human endothelial cells.

Cultered human endothelial cells from umbilical veins (HUVEC) were used and incubated for 10 minutes with flavonoids, terpenes, sterols and precursor molecules. The flavonoids tested were the isoflavone genistein, the flavonol quercetin, the epi-flavan-3-ols epicatechin, epicatechingallate, epigallocatechin, epigallocatechingallate, procyanidin and the biflavan sciadopitysin. The terpenoids tested were the diterpenes α-tocopherol and ginkgolides A, B, C, the sesquiterpene bilobalide, the triterpenes ginsenoside Rb1, Rb2, Rc, Rd, Re, Rf, Rg1 and the tetraterpene β-carotene. The sterols tested were stigmasterol, lanosterol and cholesterol. The biosynthesis precursor molecules tested were mevalonic acid, malonic acid, shikimic acid, chorismic acid and the progenitor squalene. 

Nicotine has been shown to induce endothelial dysfunction, which is an early marker of atherosclerosis. Nicotine undergoes extensive metabolism in the liver, forming a number of major and minor metabolites. There are very limited data on the effect of nicotine metabolites on the cardiovascular system. This study investigates the effects of nicotine and the nicotine metabolites, cotinine, cotinine-N-oxide, nicotine-1-N-oxide, norcotinine, trans-3-hydroxycotinine, on angiotensin-converting enzyme (ACE) in human endothelial cells. Cultured endothelial cells obtained from human umbilical cord vein (HUVECs) were stimulated with nicotine or nicotine metabolites in concentrations similar to those observed in plasma during smoking. ACE activity and expression were analyzed using commercial kits. The results showed that nicotine and nicotine metabolites can increase both activity and expression of ACE. However, a marked individual variation in the response to the drugs was observed. This variation was not associated with the ACE insertion/deletion polymorphism. Tobacco contains numerous chemical compounds, and the underlying cause for development of atherosclerosis in smokers is probably multifactorial. The results from this study could explain one cellular mechanism by which smoking exerts negative effect on the vascular system.

The effects of Ginkga bi/aba (Ginkgoaceae), its terpene-Iactones (ginkgolide A, B, C and bilobalide), biflavonols (quercetin), biflavones (sciadopitysin) and proanthocyanidins (procyanidin) on angiotensin-converting enzyme (ACE) activity and nitric oxlde (NO) production in cultured human endothelial cells from umbilical veins (HUVEC) were investigated. A dose-dependent significant inhibition of the ACE activity was observed arter 10 min incubation with Ginkga bi/aba extract EGb  761 and quercetin. No significant effects due to terpene-Iactones or sciadopitysin were seen. Incubation with Ginkga bi/aba extract, quercetin, sciadopitysin and procyanidin for 24 hr significantly Increased NO production. No significant effects were seen with ginkgollde A, B and C, while bilobalide induced a dose-dependent decrease in NO production. In conclusion, this study shows that Ginkga bi/aba extract Inhibits ACE activlty and increases NO production from HUVEC. A flavonol (quercetin and/or homologs) is the main component responsible for the inhibitory effect ofACE activity. Quercetin and a proanthocyandin (procyanidin) are responsible for the increases seen in NO production. These results may explain the positive effects of Ginkga bi/aba on the cardiovascular system and on cognitive function.

Teaching of the sciences of behaviour in higher health care education is sparse. The authors believe that students with increased knowledge and education of the human mind and soul would have a wider understanding of the human nature. Physiology describes the anatomy and function of the body, but in order to describe life/the living human, they were looking for a tool to describe the mind/soul as well as the body; to describe the connection between the two. Their intention was to teach the knowledge of the human being as an exciting experience and not just as a patient but as a larger concept; a human being in all its dimensions.

To understand the multidimensional structure of behaviour, as many perspectives as possible are needed. In using film and fiction in education, the authors want the students to use their own sensory systems and emotions to learn about behaviour. As fiction and film expose the microcosmos, the audience will experience the microcosmos in the spotlight. The purpose of this article is to stimulate and inspire other teachers to use these means in higher health care education.

Melanophores from Xenopus laevis are pigmented cells, capable of quick colour changes through cyclic adenosine 3':5'-monophosphate (cAMP) coordinated transport of their intracellular pigment granules, melanosomes. In this study we use the melanophore cell line to evaluate the effects of Panax ginseng extract G115 on organelle transport. Absorbance readings of melanophore-coated microplates, Correlate-EIA direct cAMP enzyme immunoassay kit, and western blot were used to measure the melanosome movement and changes in intracellular signalling. We show that Panax ginseng induces a fast concentration-dependent anterograde transport of the melanosomes. No significant increase in the cAMP level was seen and pre-incubation of melanophores with the protein kinase C (PKC) inhibitor EGF-R Fragment 651-658 (M-EGF) only partly decreased the ginseng-induced dispersion. We also demonstrate that Panax ginseng, endothelin-3 (ET-3) and alpha-melanocyte stimulating hormone (MSH) stimulate an activation of mitogen activated protein kinase (MAPK). Pre-incubation with M-EGF decreased the MAPK activity induced by ET-3 and MSH, but again only marginally affected the response of Panax ginseng. Thus, in melanophores we suggest that Panax ginseng stimulates an anterograde transport of pigment organelles via a non-cAMP and mainly PKC-independent pathway.

Current knowledge about vascular function stems mainly from pharmacological in vitro studies using mounted vascular strips on a strain gauge. We know of no paper that has systematically examined the possibility of assessing the conventional dose–response effects of iontophoresis and laser Doppler investigation of vasoactive substances and compared those relations to data obtained from strips mounted on a strain gauge.

We used the vasoactive substances acetylcholine (endothelium dependent) and sodium nitroprusside (endothelium independent) and an antagonist (atropine) to enable further investigations in the receptor physiology of iontophoresis.

Dose–response curves from the iontophoresis experiments showed close similarity to those obtained by vascular strips mounted on a strain gauge. The coefficient of variation (CV) of the dose–response factors found in iontophoresis (both inter and intra experimental variability) was low. The iontophoretic effective dose of 50% (ED50) for acetylcholine and nitroprusside had only CVs of 25% and 26%, respectively, compared with 71% and 77% for the vascular strips. Acetylcholine-induced response was antagonized by iontophoresis of atropine. Contrary to expectations, this antagonism was not competitive.

The results show that iontophoresis in combination with laser Doppler technology produces reproducible and reliable dose–response curves that picture the vascular effects of vasoactive drugs.

This study investigates the effects of the Panax ginseng (Araliaceae) extract G115 on angiotensin-converting enzyme (ACE) activity and nitric oxide (NO) in cultured human endothelial cells from umbilical veins (HUVEC) and bovine mesenteric arteries (BMA). In HUVEC, ACE activity was significantly reduced after 10 min incubation with aqueous extract of ginseng 5.0 and 10 mg/ml. This effect was additative with the inhibition of the traditional ACE inhibitor enalaprilat. No effect was seen on NO production from the cells. Angiotensin I-induced contraction of BMA was significantly attenuated by 0.1 and 0.5 mg/ml ginseng, while no endothelium-dependent or -independent relaxation was seen. In conclusion, extract of Panax ginseng (G115) inhibits ACE activity, but does not affect NO production in HUVEC and BMA. © 2005 Elsevier Ireland Ltd. All rights reserved.

A diversity of pharmacological effects on the cardiovascular system have been reported for Camellia sinensis: antioxidative, antiproliferative and anti-angiogenic activity, and nitric oxide synthase activation. The purpose of this study was to investigate if the connection between tea and angiotensin-converting enzyme (ACE) and nitric oxide (NO) might be an explanation of the pharmacological effects of tea on the cardiovascular system. Cultured endothelial cells from human umbilical veins (HUVEC) were incubated with extracts of Japanese Sencha (green tea), Indian Assam Broken Orange Pekoe (black tea) and Rooibos tea, respectively. The main flavanols and purine alkaloids in green and black tea were examined for their effects on ACE and NO. After incubation with green tea, black tea and Rooibos tea for 10 min, a significant and dose-dependent inhibition of ACE activity in HUVEC was seen with the green tea and the black tea. No significant effect on ACE was seen with the Rooibos tea. After 10-min incubation with (-)-epicatechin, (-)- epigallocatechin, (-)-epicatechingallate and (-)-epigallocatechingallate, a dose-dependent inhibition of ACE activity in HUVEC was seen for all four tea catechins. After 24-h incubation, a significantly increased dose-dependent effect on NO production in HUVEC was seen for the green tea, the black tea and the Rooibos tea. After 24-h incubation with (-)-epicatechin, (-)-epigallocatechin, (-)-epicatechingallate and (-)-epigallocatechingallate, a dose-dependent increased NO production in HUVEC was seen. In conclusion, tea extracts from C. sinensis may have the potential to prevent and protect against cardiovascular disease. © 2006 The Authors.

Evidence concerning the importance of angiotensin-converting enzyme (ACE) genotype in cardiovascular diseases is accumulating. The aim of this study was to investigate if nitric oxide (NO), generated from glyceryl trinitrate (GTN), affects human serum ACE activity in vivo, and if so, whether this effect was dependent on ACE genotype and (or) reflected in blood pressure reduction. A tablet containing 5 mg GTN was bucally administered for 5 minutes to 17 healthy volunteers. Blood pressure (BP) was recorded, and serum ACE activity, ACE genotype, and plasma cGMP was analyzed. GTN administration significantly reduced BP only in individuals with the deletion/deletion (DD) genotype. Sixty minutes after GTN administration, serum ACE activity was reduced in individuals with the insertion/insertion (II) and insertion/deletion (ID) genotypes, but not the DD genotype. Comparing the change in ACE activity over time between the genotypes resulted in the following: II vs. DD, p < 0.01, II vs. ID, p < 0.05, and ID vs. DD, p < 0.05. There was no significant difference in plasma cGMp content neither between the ACE genotypes nor before and after GTN administration. In conclusion, GTN inhibits serum ACE in vivo in individuals with the II and ID, but not the DD genotype. © 2005 NRC Canada.

This study investigates the effects of exogenous and endogenous nitric oxide (NO) on human circulating and endothelial angiotensin-converting enzyme activity and platelet aggregation. The NO donor S-nitroso-N-acetylpenicillamine (10-8-10-6 M) significantly and dose-dependently inhibited serum angiotensin-converting enzyme activity. The concomitant addition of S-nitroso-N-acetylpenicillamine to angiotensin-converting enzyme inhibitor-treated (captopril or enalaprilat) serum, further reduced angiotensin-converting enzyme activity. In cultured endothelial cells from human umbilical veins (HUVECs), both S-nitroso-N-acetylpenicillamine and 3-morpholinosydnonimine (SIN-1) significantly reduced angiotensin-converting enzyme activity. An additative effect was seen with a combined treatment of captopril and S-nitroso-N-acetylpenicillamine. Treatment with the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) did not affect angiotensin-converting enzyme activity. Thrombin inhibited endothelial angiotensin-converting enzyme activity, an effect that was abolished when cells were pretreated with L-NMMA. Adenosine 5'-diphosphate (ADP)-induced platelet aggregation was inhibited with S-nitroso-N-acetylpenicillamine, SIN-1 and nitroglycerine. Captopril did not affect aggregation, while a high concentration of enalaprilat (10-4 M) reduced it. The concomitant addition of 10-5 M angiotensin-converting enzyme inhibitor to NO donor-treated platelets resulted in a further reduction of platelet aggregation. This effect was most evident with SIN-1 and enalaprilat. In conclusion, both exogenous and endogenous NO inhibit human angiotensin-converting enzyme activity. NO donors and angiotensin-converting enzyme inhibitors act in concert to inhibit angiotensin-converting enzyme and platelet aggregation. Copyright (C) 2000 Elsevier Science B.V.

Cardiovascular diseases are a major cause of death in Western countries. Angiotensin-converting enzyme (ACE) is as a key enzyme in the renin-angiotensin system involved in the regulation of blood pressure, and water and electrolyte balance in the body. ACE not ouly increases the conversion of angiotensin I to the active angiotensin II, but also degrades bradykinin. ACE inhibitors, like captopril, are today first-line treatment in hypertension and heart failure.

We have shown that two structurally different ACE inhibitors, captopril and fosinopril, exhibit anti-atherosclerotic effects in hypercholesterolemic mini pigs. Captopril, but not fosinopril, improved endothelial function in the iliac arteries from the mini pigs.

Bradykinin-induced relaxation of porcine iliac arteries was mediated by bradykinin B2 receptors and the subsequent release of nitric oxide (NO). ACE inhibitors did not affect the bradykinin-induced relaxation, implying that other enzymes than ACE (e. g. carboxypeptidase M; CPM) are involved in bradykinin degradation in these vessels. Bradykinin B, and B2 receptors on the vascular media elicited a contraction mediated by cyclooxygenase metabolite(s). Treatment with captopril potentiated bradykinin B, receptor-mediated contraction, due to CPM becoming responsible for bradykinin degradation.

Captopril potentiated bradykinin- and inhibited angiotensin I-induced contractions only in arteries with intact NO synthesis. This implied that NO synthesis is necessary for an effective ACE inhibition. ACE activity analyses did reveal that both exogenous and endogenous NO are able to inhibit porcine and human ACE activity. It was also shown that this inhibition is additative with captopril and enalaprilat. This additative effect of NO and ACE inhibitors on ACE activity affected not only angiotensin I- and bradykinin- mediated contractions of porcine iliac arteries, but also reduced human platelet aggregation.

In summary, ACE inhibitors show anti-atherosclerotic properties in hypercholesterolemic mini pigs. ACE inhibitor treatment of porcine iliac arteries did not affect bradykinin-induced relaxation, but instead shunted over bradykinin to other enzymes generating the bradykinin B 1 receptor agonist desArg9 -bradykinin. NO was found to be an endogenous inhibitor of ACE, acting in concert with therapeutically used ACE inhibitors to decrease vascular tone and human platelet aggregation.

The influence of the angiotensin-converting enzyme inhibitor captopril on bradykinin-and angiotensin I-induced responses with special regard to nitric oxide (NO) was studied. Auxometric tension and angiotensin-converting enzyme activity was studied in isolated porcine iliac arteries. Captopril potentiated bradykinin-induced contraction of preparations with intact endothelium; this potentiation was not seen with the kininase I inhibitor mergepta or a bradykinin B₁-receptor antagonist. Captopril did not affect bradykinin-induced relaxation. The captopril-mediated increase of bradykinin-induced contraction was only seen in preparations with intact endothelium, while captopril did not affect arterial strips treated with Nω-nitro-L-arginine. Angiotensin I-induced contractions was less reduced by captopril when the strips were pretreated with Nω-nitro-L-arginine. Both captopril and the NO donor S-nitroso-N-acetyl-penicillamine inhibited angiotensin-converting enzyme activity. An additional reduction in angiotensin-converting enzyme activity was seen when S-nitroso-N-acetyl-penicillamine was added to captopril-treated preparations. In conclusion, captopril increased bradykinin-induced contraction in a NO-dependent manner. This potentiation is probably mediated by the increased metabolism of bradykinin by kininase I, and the additive angiotensin-converting enzyme inhibitory effect of captopril and NO.

Bradykinin-induced responses were studied in isolated porcine iliac arteries. Relaxation was endothelium dependent and seen at low concentrations (10^-10-10^-8 M) of bradykinin. It was inhibited by the bradykinin B₂-receptor antagonist icatibant (HOE-140) and by the nitric oxide synthase inhibitor N^ω-nitro-L-arginine. Bradykinin-induced relaxation was significantly potentiated by the kininase I carboxypeptidase inhibitor mergepta (10^-6 M). Bradykinin (>10^-7M) elicited contraction of preparations with or without endothelium. The contraction was abolished by indomethacin but was not affected by the thromboxane A₂/prostaglandin H₂-receptor antagonist SQ 29,548. Icatibant and the bradykinin B₁-receptor antagonist desArg⁹[Leu⁸]bradykinin significantly decreased bradykinin-induced contraction regardless of endothelial function. The contraction also was decreased by treatment with mergepta. The bradykinin B₁-receptor agonist desArg⁹-bradykinin contracted endothelium-denuded arterial strips. This contraction was significantly decreased by desArg⁹ [Leu⁸] bradykinin but not by icatibant. The desArg⁹-bradykinin-induced contraction also was inhibited by the protein-synthesis inhibitor cycloheximide. Neither bradykinin-induced relaxation nor contraction was affected by the ACE inhibitors enalaprilat or cilazaprilat. In conclusion, bradykinin-induced relaxation of isolated porcine iliac arteries was mediated by endothelial bradykinin B₂ receptors and mainly nitric oxide. Bradykinin-induced contraction was endothelium independent, indomethacin sensitive, and probably mediated by bradykinin B₁ (inducible) and B₂ receptors located in the vascular smooth-muscle layer. Kininase I carboxypeptidase, and not ACE, is the main enzyme responsible for bradykinin degradation in these vessels.

We evaluated the two angiotensin-converting enzyme (ACE) inhibitors captopril and fosinopril with regard to possible antiatherosclerotic effects in minipigs. Experimental hypercholesterolemia and atherosclerosis was produced in 33 minipigs of the Gottingen strain by an egg yolk/cholesterol-enriched diet for 1 year. One group (n = 11) was fed the atherogenic diet alone and served as a control. A second group (n = 11) received captopril (80 mg/kg/day) added to the atherogenic diet, and a third group (n = 11) was treated in the same manner but with fosinopril (8 mg/kglday). The drug treatments produced significant reduction in serum ACE activity associated with a reactive increase in plasma renin activity (PRA), but had only minor effects on plasma lipids and lipoproteins. At the end of the treatment period, all animals were killed and examined for degree of atherosclerosis. The percentage of atherosclerotic area in the abdominal aorta was significantly lower in both drug-treated groups as compared with controls. Furthermore, accumulation of cholesterol in the thoracic and abdominal aorta was inhibited by drug treatment. Finally, the percentage of intimal thickening in abdominal aorta was significantly reduced in the drug-treated groups. In conclusion, the ACE inhibitors captopril and fosinopril inhibited development of atherosclerosis in hypercholesterolemic minipigs.

Background: Polymorphism in the angiotensin-converting enzyme gene (ACE I/D polymorphism) is associated with the level of ACE in plasma. However, there are large variations in plasma ACE level among individuals with the same genotype. Furthermore, ACE D/D genotype has been associated with increased risk for cardiovascular disease. The aim of this study was to investigate variations in plasma ACE levels in order to elucidate the associations between circulating ACE levels, ACE genotype, known cardiovascular risk factors and cardiovascular diseases (CVDs).

Methods and Results: Plasma ACE levels and ACE genotype were analysed in a Swedish population consisting of 672 elderly men and women. Association between ACE-genotype, levels of circulating ACE and known cardiovascular risk factors and CVDs were analyzed. The results showed increased plasma ACE levels in individuals with hypertension (p=0.003), ischemic heart disease (p=0.03), in smokers (p=0.011) and in individuals with heredity for CVDs (p=0.031). Furthermore, treatment with ACE inhibitors increased the level of ACE in plasma (p<0.001). No association was found between D/D genotype and CVD. Instead, ischemic heart disease was more frequent among carriers of the I/I genotype (p=0.009).

Conclusion: Although plasma ACE levels are strongly influenced by ACE genotype, there are large variations in plasma ACE level among carriers of the same genotype. Our data does not support an association between ACE D/D polymorphism and CVDs but indicates an association to increased level of ACE in the circulation, suggesting that ACE level rather than ACE genotype is the crucial factor associated with risk for CVDs.

This study investigates the effects of exogenous and endogenous nitric oxide (NO) on human circulating and endothelial angiotensin-converting enzyme (ACE) activity, and platelet aggregation. The NO donor S-nitroso N-acetylpenicillamine SNAP (10^-8-10^-6 M) significantly and dose-dependently inhibited serum ACE activity. The concomitant addition of SNAP to ACE inhibitor-treated (captopril or enalaprilat) serum, further reduced ACE activity. In cultured endothelial cells from human umbilical veins (HUVEC), both SNAP and 3-morpholinosydnonimine (SIN-1) significantly reduced ACE activity. An additative effect was seen with a combined treatment of captopril and SNAP. Treatment with the NO synthase inhibitor N^G-monomethyl-L-arginine (L-NMMA) did not affect ACE activity. Thrombin inhibited endothelial ACE activity, an effect that was abolished when cells were pretreated with L-NMMA. ADP-induced platelet aggregation was inhibited with SNAP, SIN-1 and nitroglycerine (GTN). Captopril did not affect aggregation, while a high concentration of enalaprilat (10^-4 M) reduced it. The concomitant addition of 10^{-5 M} ACE inhibitor to NO donor-treated platelets resulted in a further reduction of platelet aggregation. This effect was most evident with SIN-I and enalaprilat. In conclusion, both exogenous and endogenous NO inhibit human ACE activity. NO donors and ACE inhibitors act in concert to inhibit ACE and platelet aggregation.