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 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.
Zappellini
A
A
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Brazil.
Teixeira
S A
SA
Muscará
M N
MN
Zatz
R
R
Antunes
E
E
De Nucci
G
G
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002216:Captopril / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology; D004285:Dogs; D004656:Enalapril / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D004656:Enalapril; C065679:icatibant; D002216:Captopril; D019001:Nitric Oxide Synthase; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester