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

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 AT<sub>2</sub> 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<sup>G</sup> 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<sub>ATP</sub> channel blocker, did not affect intra-renal hemodynamics elicited by AII. Blockade of AT<sub>2</sub> 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 AT<sub>2</sub> 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 AT<sub>1</sub>-mediated reduction in CBF but an AT<sub>2</sub>-mediated increase in MBF. The AT<sub>2</sub> receptor-mediated increase in MBF involves guanylase cyclase, NO and dilator prostanoids but not K<sub>ATP</sub> channels

Pressor and renal regional hemodynamic effects of urotensin II in neonatal pigs

“…Changes in renal CBF are not always replicated in the medullary or papillary regions because medullary hemodynamics can be regulated independently of renal CBF (Pallone et al 1990, Navar et al 1996, Mattson 2003. Vasoactive agents, including AngII, dopamine, arginine vasopressin, atrial natriuretic peptide, and bradykinin have been demonstrated to induce renal region-specific hemodynamic changes (Takezawa et al 1987, Pallone et al 1990, Nobes et al 1991, Mattson & Cowley 1993, Heyman et al 1995, Badzynska et al 2002, Igbe et al 2012. However, the effect of UII on regional RBF was unclear.…”

Effects of fumarate on renal vascular reactivity and the modulation of blood pressure in normotensive rats: Possible contribution of the nitric oxide synthase-nitric oxide system

“…The animal was allowed a 45-minute equilibration before the commencement of drug administrations. Blood pressure returned to baseline in-between drug administrations (Igbe et al 2012). The drugs were administered as follows: fumarate (0.1, 0.3, and 1 µg/kg), sodium nitroprusside (10, 30, and 100 µg/ kg) or PMA (1, 3, and 10 µg/kg).…”