Interactions of the renin-angiotensin system and alpha-1 adrenoceptors on renal hemodynamics in healthy and acute renal failure rats: the role of nitric oxide.
The renin-angiotensin (RAS) and the alpha1 sympathetic nervous system (SNS) interact at different levels in cardiovascular regulation. Concurrent use of angiotensin-converting enzyme (ACE) inhibitors and alpha1 receptor antagonists result in a synergistic antihypertensive action and is of wide utility in cardiovascular therapy. We examined the impact of concurrent inhibition of RAS (captopril or losartan) and the SNS (prazosin) before and after acute nitric oxide (NO) synthase inhibition with L-nitro-L-arginine methyl ester (L-NAME) on renal cortical perfusion (RCF) and blood pressure (MAP) in healthy and acute ischemic renal failure (ARF) rats (n = 6). Captopril or losartan reduced MAP and increased RCF more in healthy (p < 0.001) and ARF rats (p < 0.02). Prazosin alone reduced both MAP and RCF (p < 0.001). The combination of prazosin with captopril or losartan caused an additive fall in MAP, and mitigated the fall in RCF. Captopril + prazosin caused a profound fall in RCF following L-NAME, in healthy but not ARF rats (p < 0.001). Acetylcholine (Ach), a vasodilator which stimulates endogenous NO production caused a profound paradoxical fall in RCF in ARF, but not in healthy rats (p < 0.001 ANOVA). These results indicate a significant interaction between angiotensin II and phenylephrine in renal vasomotion. It establishes that endogenous NO homeostatically opposes angiotensin II-alpha1-mediated renal vasoconstriction, and that the vasodilator role of NO is diminished in ARF. The paradoxical fall in RCF induced by Ach in ARF is speculated to result, at least in part, from the formation of peroxynitrite (ONOO-), which acts as a renal vasoconstrictor, following the combination of ischemia-generated super oxide anion (O-2), with endothelial NO released by Ach.
Ajayi AAL
Center for Cardiovascular Diseases, College of Pharmacy & Health Sciences, Texas Southern University, Houston 77004, USA. adeajayi@aol.com
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D000109:Acetylcholine / Q000037:antagonists & inhibitors; D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000503:physiopathology; D058668:Adrenergic alpha-1 Receptor Antagonists; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology
D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine