Non-contribution of renin-angiotensin system to pressor response to N(G)-nitro-L-arginine in dogs.
Acute systemic blockade of nitric oxide (NO) production by nonselective inhibitors of NO synthase (NOS) isoforms, including N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-nitro-L-arginine (L-NNA), has been shown to produce a long-lasting pressor response in conscious and anaesthetised animals. The present study was undertaken to clarify whether the renin-angiotensin system contributes to the development of this pressor response to L-NNA. Systemic blood pressure and heart rate were continuously monitored in dogs anaesthetised with pentobarbital. Plasma renin activity in the blood obtained from a femoral artery and a renal vein was measured by use of radioimmunoassay. The acute pressor response produced by the intravenous administration of L-NNA was accompanied by reduced renin activity in both systemic and renal vascular beds. Captopril, an angiotensin converting enzyme inhibitor, counteracted the pressor response to L-NNA, whereas candesartan, an angiotensin AT1-receptor antagonist, had no apparent effect on it. The counteraction by captopril of the L-NNA-induced pressor response was likely to be attributable to enhancement by captopril of depressor responses to bradykinin, as HOE-140, a bradykinin B2 receptor antagonist, neutralised the effect of captopril. These results suggest that the pressor response acutely produced by the intravenous injection of a NOS inhibitor is not mediated by the renin-angiotensin system in anaesthetised dogs.
Ishikawa
Tomohisa
T
Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka.
Nejishima
Hiromasa
H
Imamura
Takuya
T
Nakayama
Koichi
K
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects*; D001919:Bradycardia / Q000139:chemically induced; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D019335:Nitroarginine / Q000494:pharmacology*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D013237:Stereoisomerism; D013777:Tetrazoles / Q000494:pharmacology
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D013777:Tetrazoles; D019335:Nitroarginine; D001120:Arginine; D002216:Captopril; D012083:Renin; C081643:candesartan; D001920:Bradykinin