In vivo B2-receptor-mediated negative chronotropic effect of bradykinin in canine sinus node.
The chronotropic response to bradykinin (BK) injected into the sinus node artery was evaluated in anesthetized dogs. The animals (n = 14) were vagotomized and pretreated with propranolol (1 mg/kg i.v.) to prevent baroreceptor-mediated effects. Dose-dependent decreases in heart rate (from 2.4 +/- 1.3% for 1 microgram of BK to 13.1 +/- 3.7% for 10 micrograms of BK), as well as a significant fall in systemic systolic and diastolic blood pressures, were observed. Captopril (2 mg/kg i.v.) caused significant decreases in systolic (from 117 +/- 11 to 77 +/- 12 mmHg, P < 0.001) and diastolic (from 87 +/- 8 to 52 +/- 8 mmHg, P < 0.001) blood pressures but had no effect on heart rate. Converting-enzyme inhibition potentiated the BK-induced bradycardia. The new potent B2-receptor antagonist, HOE 140 (100 micrograms), significantly blocked the BK-induced chronotropic effect, whereas desArg9-BK, a B1-receptor agonist, was without effect. Prostaglandin involvement was excluded, since pretreatment with indomethacin did not prevent the bradycardia. In conclusion, in vivo BK induces a direct negative chronotropic effect, which is potentiated by converting-enzyme inhibition and is mediated by the B2-receptors independently of the prostaglandins.
Ribuot
C
C
Research Center, Hôpital du Sacré-Coeur de Montréal, Canada.
Godin
D
D
Couture
R
R
Regoli
D
D
Nadeau
R
R
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D011311:Pressoreceptors / Q000502:physiology; D018002:Receptors, Bradykinin / Q000502:physiology*; D012849:Sinoatrial Node / Q000187:drug effects*; D014628:Vagotomy
D000319:Adrenergic beta-Antagonists; D018002:Receptors, Bradykinin; D001920:Bradykinin