Pharmacology & Pharmacy, 2012, 3, 388-396 Published Online October 2012 (
Differential Effects of Angiotensin II on Intra-Renal
Hemodynamics in Rats; Contribution of Prostanoids, NO
and K+ Channels
Ighodaro Igbe1*, Eric K. I. Omogbai1, Adebayo O. Oyekan2
1Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Benin City, Nigeria; 2Center for Cardio-
vascular Diseases, College of Pharmacy and Health Sciences, Texas Southern University, Houston, USA.
Email: *
Received May 22nd, 2012; revised June 24th, 2012; accepted July 15th, 2012
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 µg/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. NG nitro-L-arginine (L-NNA), an inhibitor of NO synthase (100 mg/L in drinking water) en-
hanced 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 KATP 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 differen-
tial 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 KATP channels.
Keywords: Angiotensin II; Hemodynamics; Medullary Blood Flow; AT2 Receptors; Prostanoids
1. Introduction
The intrarenal vasculature can respond to neural and a
variety of humoral stimuli with vasodilatation or vaso-
constriction, resulting in increased or decreased perfusion
of renal tissue, respectively [1]. Such responses may
have more serious functional consequences within the
medulla than in the cortex. This is of major physiological
and pathophysiological importance as the medulla is
widely viewed as having a crucial role in maintaining
body fluid homeostasis and in the control of arterial pres-
sure [2].
The renin-angiotensin system is a coordinated hormonal
cascade important to the regulation of renal sodium ex-
cretion and blood pressure. The major effector peptide,
angiotensin II (AII), binds to two major receptors; AT1
and AT2. While the majority of AII actions are mediated
via the AT1 receptor, evidence has accumulated that the
AT2 receptor opposes the AT1 receptor, especially by
inducing vasodilation instead of vasoconstriction and
may be important in the regulation of blood pressure and
renal function by counterbalancing the vasoconstrictor
and antinatriuretic actions of AT1 receptors [3]. However,
the roles of AT1 and AT2 receptors in regulating regional
kidney perfusion remain unclear. In rats and rabbits,
infusions of AII reduced total renal blood flow (RBF)
and cortical blood flow but have a lesser effect on
medullary blood flow [4,5]. AII can even increase MBF,
especially when administered as a bolus [1,6]. Many
studies have demonstrated that the medullary vasculature
was poorly sensitive to the vasoconstrictor effects of AII
*Corresponding author.
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Contribution of Prostanoids, NO and K+ Channels
Copyright © 2012 SciRes. PP
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