Direct effects in vivo of angiotensins I and II on the canine sinus node.
The chronotropic responses to angiotensins I and II (5 micrograms in 1 mL Tyrode's solution) injected into the sinus node artery were assessed before and after the intravenous administration of captopril (2 mg/kg) and saralasin (20 micrograms/kg) in anaesthetized dogs. The effects of angiotensin II given intravenously were also observed. The animals (n = 8) were vagotomized and pretreated with propranolol (1 mg/kg, i.v.) to prevent baroreceptor-mediated responses to increases in blood pressure. Injection of angiotensin I into the sinus node artery induced significant increases in heart rate (114 +/- 6 vs. 133 +/- 6 beats/min) and in systemic systolic (134 +/- 13 vs. 157 +/- 14 mmHg; 1 mmHg = 133.3 Pa) and diastolic (95 +/- 10 vs. 126 +/- 13 mmHg) blood pressures. Similar results were obtained when angiotensin II was injected into the sinus node artery, but intravenous injection induced changes in systolic (138 +/- 8 vs. 180 +/- 25 mmHg) and diastolic (103 +/- 8 vs. 145 +/- 20 mmHg) blood pressures only. Captopril induced a significant decrease in systolic (118 +/- 11 vs. 88 +/- 12 mmHg) and diastolic (84 +/- 9 vs. 59 +/- 9 mmHg) blood pressures without affecting the heart rate (109 +/- 6 vs. 106 +/- 6 beats/min). Saralasin produced a significant increase in systolic (109 +/- 7 vs. 126 +/- 12 mmHg) blood pressure only. Increments in heart rate and systolic and diastolic blood pressures in response to angiotensins I and II were, respectively, abolished by captopril and saralasin. It was concluded that angiotensin II has, in vivo, a direct positive chronotropic effect that can be blocked by saralasin.(ABSTRACT TRUNCATED AT 250 WORDS)
Research Centre, Hôpital du Sacré-Coeur de Montréal, Qué., Canada.
C
C
Lambert
D
D
Godin
P
P
Fortier
R
R
Nadeau
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012504:Saralasin / Q000494:pharmacology; D012849:Sinoatrial Node / Q000187:drug effects*; D014628:Vagotomy
D000319:Adrenergic beta-Antagonists; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D012504:Saralasin