Differential Effects of Angiotensin II on Intra-Renal Hemodynamics in Rats; Contribution of Prostanoids, NO and K⁺ Channels

Ighodaro Igbe, Eric.K.I. Omogbai, Adebayo.O. Oyekan

Center for Cardiovascular Diseases, College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Nigeria.

DOI: 10.4236/pp.2012.34052                

Abstract

Many agents are known to cause qualitative and quantitative differences in intrarenal blood flow. This study tested the hypothesis that angiotensin II (AII) evokes a differential effect on cortical (CBF) and medullary blood flow (MBF) and that AT₂ receptor mediates AII-induced increase in renal MBF by mechanisms related to nitric oxide (NO) and prostanoids. AII (100, 300 and 1000 ng/kg/min) increased mean arterial blood pressure (MABP) by 24% ± 7% (p < 0.05); decreased CBF by 30% ± 2% (p < 0.05); but increased MBF by 21% ± 8% (p < 0.05). Indomethacin (5 mg/kg), enhanced AII effects on MABP by 154% ± 26% (p < 0.05), MBF by 141% ± 46 % but decreased CBF by 74% ± 54% (p < 0.05) indicating the involvement of dilator prostanoids in the systemic and medullary circulation but constrictor prostanoids in the cortex. N^G nitro-L-arginine (L-NNA), an inhibitor of NO synthase (100 mg/L in drinking water) enhanced AII effects on MABP (169 ± 75, p < 0.05) and decreased CBF (107% ± 50%, p < 0.05) but blunted the effects of AII on MBF (150% ± 21%, p < 0.05). 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ; 2 mg/kg), a guanylyl cyclase inhibitor, enhanced AII effects on MABP (118% ± 32% , p < 0.05) and decreased CBF(85% ± 47% , p < 0.05) but blunted the effects of AII on MBF (96% ± 15%, p < 0.05). However, glibenclamide (20 μg/kg), a K_ATP channel blocker, did not affect intra-renal hemodynamics elicited by AII. Blockade of AT₂ receptors with PD123319 (50 μg/kg/min) did not change basal or AII-induced changes MABP or CBF but blunted AII-induced increase in MBF by 60% ± 11 % (p < 0.05). CGP42112 (10 μg/kg/min), an AT₂ receptor agonist, elicited a reduction in MABP and increases in CBF and MBF that were abolished or attenuated by PD123319. These findings demonstrate that AII elicited differential changes in intrarenal blood flow; an AT₁-mediated reduction in CBF but an AT₂-mediated increase in MBF. The AT₂ receptor-mediated increase in MBF involves guanylase cyclase, NO and dilator prostanoids but not K_ATP channels.

Keywords

Angiotensin II; Hemodynamics; Medullary Blood Flow; AT₂ Receptors; Prostanoids

Conflicts of Interest

The authors declare no conflicts of interest.

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