Angiotensin II Type 2 Receptors and Nitric Oxide Sustain Oxygenation in the Clipped Kidney of Early Goldblatt Hypertensive Rats
2008 (English)In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 51, no 2, 345-351 p.Article in journal (Refereed) Published
Angiotensin-converting enzyme inhibitors (ACEIs) decrease theglomerular filtration rate and renal blood flow in the clippedkidneys of early 2-kidney, 1-clip Goldblatt hypertensive rats,but the consequences for oxygenation are unclear. We investigatedthe hypothesis that angiotensin II type 1 or angiotensin IItype 2 receptors or NO synthase mediate renal oxygenation responsesto ACEI. Three weeks after left renal artery clipping, kidneyfunction, oxygen (O2) use, renal blood flow, renal corticalblood flow, and renal cortical oxygen tension (PO2) were measuredafter acute administration of an ACEI (enalaprilat) and afteracute administration of ACEI following acute administrationof an angiotensin II type 1 or angiotensin II type 2 receptorblocker (candesartan or PD-123,319) or an NO synthase blocker(NG-nitro-L-arginine methyl ester with control of renal perfusionpressure) and compared with mechanical reduction in renal perfusionpressure to the levels after ACEI. The basal renal corticalPO2 of clipped kidneys was significantly lower than contralateralkidneys (35±1 versus 51±1 mm Hg; n=40 each). ACEIlowered renal venous PO2, cortical PO2, renal blood flow, glomerularfiltration rate, and cortical blood flow and increased the renalvascular resistance in the clipped kidney, whereas mechanicalreduction in renal perfusion pressure was ineffective. PD-123,319and NG-nitro-L-arginine methyl ester, but not candesartan, reducedthe PO2 of clipped kidneys and blocked the fall in PO2 withacute ACEI administration. In conclusion, oxygen availabilityin the clipped kidney is maintained by angiotensin II generation,angiotensin II type 2 receptors, and NO synthase. This disclosesa novel mechanism whereby angiotensin can prevent hypoxia ina kidney challenged with a reduced perfusion pressure.
Place, publisher, year, edition, pages
2008. Vol. 51, no 2, 345-351 p.
Goldblatt hypertension, renal oxygen tension, renal blood flow, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-99299DOI: 10.1161/HYPERTENSIONAHA.107.097832PubMedID: 18158356OAI: oai:DiVA.org:liu-99299DiVA: diva2:657234