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 the glomerular filtration rate and renal blood flow in the clipped kidneys of early 2-kidney, 1-clip Goldblatt hypertensive rats, but the consequences for oxygenation are unclear. We investigated the hypothesis that angiotensin II type 1 or angiotensin II type 2 receptors or NO synthase mediate renal oxygenation responses to ACEI. Three weeks after left renal artery clipping, kidney function, oxygen (O2) use, renal blood flow, renal cortical blood flow, and renal cortical oxygen tension (PO2) were measured after acute administration of an ACEI (enalaprilat) and after acute administration of ACEI following acute administration of an angiotensin II type 1 or angiotensin II type 2 receptor blocker (candesartan or PD-123,319) or an NO synthase blocker (NG-nitro-L-arginine methyl ester with control of renal perfusion pressure) and compared with mechanical reduction in renal perfusion pressure to the levels after ACEI. The basal renal cortical PO2 of clipped kidneys was significantly lower than contralateral kidneys (35±1 versus 51±1 mm Hg; n=40 each). ACEI lowered renal venous PO2, cortical PO2, renal blood flow, glomerular filtration rate, and cortical blood flow and increased the renal vascular resistance in the clipped kidney, whereas mechanical reduction in renal perfusion pressure was ineffective. PD-123,319 and NG-nitro-L-arginine methyl ester, but not candesartan, reduced the PO2 of clipped kidneys and blocked the fall in PO2 with acute ACEI administration. In conclusion, oxygen availability in the clipped kidney is maintained by angiotensin II generation, angiotensin II type 2 receptors, and NO synthase. This discloses a novel mechanism whereby angiotensin can prevent hypoxia in a 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:uu:diva-13119DOI: 10.1161/HYPERTENSIONAHA.107.097832PubMedID: 18158356OAI: oai:DiVA.org:uu-13119DiVA: diva2:40889