In vivo inhibition of nitric oxide synthesis does not depend on renin-angiotensin system activation

Abstract

The role of the renin-angiotensin system in the haemodynamic changes induced by acute administration of N omega-nitro-L-arginine methyl ester in anaesthetised dogs was investigated. The left femoral artery and vein were cannulated for blood pressure measurement and drug administration, respectively. A Swan-Ganz catheter was introduced through the right femoral vein and advanced to the pulmonary artery. Pulmonary arterial pressure, right atrial pressure and cardiac output were also determined. N omega-Nitro-L-arginine methyl ester (0.01-10.0 mg/kg) was administered alone (control animals, n = 18) or in the presence of the angiotensin-converting enzyme inhibitors, captopril (2 mg/kg, n = 9) or enalapril (2 mg/kg, n = 7) or of the bradykinin B2 receptor antagonist D-[Arg-Hyp3, Thi5, D-Tic7, Oic8]bradykinin (Hoe 140, 0.1 mg/kg, n = 6). Cerebellum nitric oxide synthase and serum angiotensin-converting enzyme activities were also measured. N omega-Nitro-L-arginine methyl ester induced dose-dependent increases in blood pressure and systemic vascular resistance and decreases in heart rate and cardiac output. Nitric oxide synthase activity was inhibited 58% by N omega-nitro-L-arginine methyl ester (from 3.37 +/- 0.30 to 1.40 +/- 0.24 pmol/min per mg protein, P < 0.05, n = 5). Both enalapril and captopril potentiated the cardiovascular changes induced by bradykinin (300 ng/kg, bolus). Moreover, enalapril inhibited angiotensin-converting enzyme activity from 12.8 +/- 1.2 to 1.1 +/- 0.2 nmol/ml per min (P < 0.05, n = 6). Under these conditions, N omega-nitro-L-arginine methyl ester administration elicited the same haemodynamic changes as those observed in non-treated animals, except for preventing the decrease in systolic index. Hoe 140 had no effect on the cardiovascular responses to N omega-nitro-L-arginine methyl ester. These results indicate that the renin-angiotensin system does not modulate these haemodynamic changes.