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The Rho-kinase inhibitor Y27632 promotes ureteral relaxation in an in vivo rat model for partial ureteral obstruction
IRCCS Osped San Raffaele, Italy.
Ludwig Maximilians Univ Munchen, Germany.
ASST Sette Laghi, Italy.
Kings Coll Hosp London, England.
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2023 (English)In: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726, Vol. 41, p. 2541-2547Article in journal (Refereed) Published
Abstract [en]

PurposeAim of this study was to evaluate the effect of intravenous Y27632 (a ROK inhibitor) on intra-ureteral pressures and on blood pressure in an in vivo rat model for unilateral partial ureteral obstruction (PUO).Methods15 Male Sprague Dawley rats were used. Under isofluran anesthesia, saline was continuously infused via polyethylene (PE)-10 catheters inserted in the ureters beneath the kidney pelvis. Left psoas muscle was sutured around the distal left ureter to create a partial obstruction. Carotid artery and femoral vein were cannulated with PE catheters for registration of mean arterial blood pressure (MAP) and for administration of drugs. Left and right ureter pressures and MAP were simultaneously recorded. Y27632 (0.03 and 0.1 mg/kg each n = 6-7) was given intravenously. T-test was used for comparisons.ResultsSpontaneous peristaltic pressure waves were recorded at baseline for both ureters. After the obstruction, Y27632 reduced maximum pressure (MaxP) by 10.5 +/- 1.9% (0.03 mg/kg; p = 0.004) and 29.1 +/- 4.8% (0.1 mg/kg; p < 0.001), minimum pressure (MinP) by 5.2 +/- 2.3% (0.03 mg/kg; p = 0.02) and 12.2 +/- 3.4% (0.1 mg/kg; p = 0.009), the area under the curve (AUC) by 7.8 +/- 2.4% (0.03 mg/kg; p = 0.008) and 16.5 +/- 3.7% (0.1 mg/kg;p = 0.007), the waves amplitude by 23.4 +/- 11.3% (0.03 mg/kg; p = 0.098) and 38.7 +/- 7.5% (0.1 mg/kg; p < 0.001), with no effect on contraction frequency. During simultaneous recordings from the normal ureter at the investigated doses, Y27632 reduced MaxP, MinP, AUC and waves amplitude by 1-7%. The MAP was reduced by 12.5 +/- 5.3% (0.03 mg/kg; p = 0.07) and 15.8 +/- 1.8% (0.1 mg/kg; p < 0.001).ConclusionsY27632 decreased intra-ureteral pressures of a partially obstructed ureter with limited effect on blood pressure in an animal model of unilateral PUO.

Place, publisher, year, edition, pages
SPRINGER , 2023. Vol. 41, p. 2541-2547
Keywords [en]
Ureter; Urolithiasis; Ureteral pressure; In vivo; Rho-kinase; Antagonist
National Category
Urology and Nephrology
Identifiers
URN: urn:nbn:se:liu:diva-199144DOI: 10.1007/s00345-023-04528-3ISI: 001093250400001PubMedID: 37528287OAI: oai:DiVA.org:liu-199144DiVA, id: diva2:1811851
Note

Funding Agencies|Urological Research Institute; Gester Foundation

Available from: 2023-11-14 Created: 2023-11-14 Last updated: 2024-04-09

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Division of Clinical Chemistry and PharmacologyFaculty of Medicine and Health SciencesDepartment of Clinical Pharmacology
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