Coronary effects of exogenous and endogenous bradykinin in conscious dogs.
The effects of intravenous (iv) bolus administrations of bradykinin (0.1-1 microgram.kg-1) on large and small coronary arteries were investigated in seven chronically instrumented conscious dogs. Bradykinin dose-dependently increased heart rate, left ventricular dP/dt max, coronary blood flow and coronary artery diameter and decreased aortic pressure. Subchronic inhibition of the nitric oxide synthase (NOS) pathway (N omega-nitro-L-arginine, 20 mg.kg-1.d-1 during 7 days) attenuated the systemic and coronary effects of bradykinin. HOE 140, a specific bradykinin B2 receptor antagonist, administered at a dose (30 micrograms/kg) sufficient to completely inhibit the systemic and coronary effects of exogenous bradykinin (1 microgram/kg, iv bolus), had no effect on baseline systemic and coronary hemodynamic parameters. HOE 140 had also no effect on the flow-dependent increase in large coronary artery diameter and on the relationship between flow debt and flow repayment volumes observed during myocardial reactive hyperemia. This lack of effect of HOE 140 persisted when experiments were repeated after NOS inhibition. We conclude that (a) exogenous bradykinin dilates large and small coronary arteries through a partially NO-mediated mechanism, and (b) endogenous bradykinin plays no role in the control of arterial pressure, heart rate, LV dP/dt max, basal and flow-stimulated coronary hemodynamics, both in control conditions and after subchronic inhibition of NOS in the conscious dog.
Puybasset
L
L
Département de Pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France.
Giudicelli
J F
JF
Berdeaux
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001810:Blood Volume / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D006940:Hyperemia / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D065168:Bradykinin Receptor Antagonists; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; C065679:icatibant; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin; D000109:Acetylcholine; D001920:Bradykinin