Mechanisms of kinin B1-receptor-induced hypotension in the anesthetized dog.
Our study was performed to investigate the mechanism underlying the phypotensive effect of kinin B1-receptor activation with des-Arg9-bradykinin (des-Arg9-BK), in comparison with B2-receptor activation with bradykinin (BK), in anesthetized dogs. Bolus intravenous and intraarterial injections of both kinins were compared. BK (0.6 microgram/kg) produced a transient hypotension of the same magnitude, regardless of the route of administration (from 110 +/- 6 mm Hg to 66 +/- 6 mm Hg, or -41 +/- 5%). In contrast, intraarterial injection of des-Arg9-BK (0.6 microgram/kg) induced a weaker hypotension compared with its intravenous injection (-27 +/- 2% vs. -39 +/- 3%, p < 0.05). The hypotension induced by both kinins was accompanied by increases in heart rate, maximum left ventricular dP/dt, and aortic blood flow, suggesting a reduction in peripheral resistance. The positive inotropic and chronotropic effects of BK and des-Arg9-BK were found to be mediated by the sympathetic nervous system, because they were abolished by propranolol. The hypotension induced by intravenous and intraarterial injections of BK and intravenous injections of des-Arg9-BK was only slightly reduced after nitric oxide (NO) synthase inhibition with NG-nitro-L-arginine (L-NNA). In contrast, the hypotensive effect of intraarterial injection of des-Arg9-BK was reduced by half after treatment with L-NNA (p < 0.05). Neither bilateral vagotomy nor ganglionic blockade with pentolinium reduced the hypotension induced by both kinins. In conclusion, the hypotensive effect of des-Arg9-BK and BK results from a peripheral vasodilation. The contribution of NO in this vasodilation is substantial for des-Arg9-BK when administered intraarterial but limited for BK and intravenous des-Arg9-BK.
Lamontagne
D
D
Centre de recherche, Hôpital du Sacré-Coeur de Montréal, Québec, Canada.
Nakhostine
N
N
Couture
R
R
Nadeau
R
R
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin / Q000819:agonists / Q000502:physiology*; D014628:Vagotomy
D004791:Enzyme Inhibitors; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin; C024626:bradykinin, des-Arg(9)-; D019335:Nitroarginine; D009569:Nitric Oxide; D001920:Bradykinin