IN-VIVO INHIBITION OF NITRIC-OXIDE SYNTHESIS DOES NOT DEPEND ON RENIN-ANGIOTENSIN SYSTEM ACTIVATION

The role of the renin-angiotensin system in the haemodynamic changes i nduced by acute administration of N-omega-nitro-L-arginine methyl este r in anaesthetised dogs was investigated. The left femoral artery and vein were cannulated for blood pressure measurement and drug administr ation, respectively. A Swan-Ganz catheter was introduced through the r ight femoral vein and advanced to the pulmonary artery. Pulmonary arte rial pressure, right atrial pressure and cardiac output were also dete rmined. N-omega-Nitro-L-arginine methyl ester (0.01-10.0 mg/kg) was ad ministered alone (control animals, n = 18) or in the presence of the a ngiotensin-converting enzyme inhibitors, captopril (2 mg/kg, n = 9) or enalapril (2 mg/kg, n = 7) or of the bradykinin B-2 receptor antagoni st D-[Arg-Hyp(3),Thi(5),D-Tic(7),Oic(8)]bradykinin (Hoe 140, 0.1 mg/kg , n = 6). Cerebellum nitric oxide synthase and serum angiotensin-conve rting enzyme activities were also measured. N-omega-Nitro-L-arginine m ethyl ester induced dose-dependent increases in blood pressure and sys temic vascular resistance and decreases in heart rate and cardiac outp ut. 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 captopriI potenti ated the cardiovascular changes induced by bradykinin (300 ng/kg, bolu s). Moreover, enalapril inhibited angiotensin-converting enzyme activi ty from 12.8 +/- 1.2 to 1.1 +/- 0.2 nmol/ml per min (P < 0.05, it = 6) . Under these conditions, N-omega-nitro-L-arginine methyl ester admini stration elicited the same haemodynamic changes as those observed in n on-treated animals, except for preventing the decrease in systolic ind ex. Hoe 140 had no effect on the cardiovascular responses to N-omega-n itro-L-arginine methyl ester. These results indicate that the renin-an giotensin system does not modulate these haemodynamic changes.