Role of endogenous angiotensin II in renal hemodynamic and excretory responses to L-arginine infusion.
The purpose of this study was to investigate whether endogenous angiotensin II has a functional role in renal hemodynamic and excretory changes induced by L-arginine, a substrate for nitric oxide (NO), in anesthetized rats. During the intravenous infusion of L-arginine (50, 100, 200 mumol/kg.min), there was no significant change in systemic or renal hemodynamics, but urine flow and urinary sodium excretion markedly increased in a dose-dependent manner. Simultaneously, L-arginine infusion produced an increase in urinary excretion of NO metabolites, NO2- and NO3-. Treatment with L-158809 ¿5,7-dimethyl-2-ethyl-3-[[2'-(1H-tetrazol-5-yl) [1,1']-biphenyl-4-yl]methyl]-3H-imidazo[4,5-b]pyridine¿ (0.3 mg/kg), a selective angiotensin II type I receptor antagonist, caused a reduction in mean arterial pressure, and a rise in renal blood flow and glomerular filtration rate, with no changes in excretory responses. In the presence of L-158809, L-arginine-induced diuretic and natriuretic actions were observed to the same extent as seen in the absence of L-158809. These data suggest that the infusion of L-arginine causes diuresis and natriuresis, possibly via the formation of nitric oxide in the kidney, and that endogenous angiotensin II is not involved in the L-arginine-induced renal actions.
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
K
K
Urabe
Y
Y
Matsumura
H
H
Nonaka
M
M
Nishiura
K
K
Maeda
S
S
Morimoto
D000758:Anesthesia; D000804:Angiotensin II / Q000378:metabolism / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D009569:Nitric Oxide; C070967:L 158809; D001120:Arginine