Mechanism of the chronotropic effects of prostacyclin in the dog: comparison with the actions of prostaglandin E2.
The cardiovascular effects of prostaglandin (PG) I2 and E2 were investigated in the anesthetized dog and in the isolated blood perfused canine atrial preparation cross-circulated by the donor dog. When small doses of PGI2 (less than .01 microgram/kg) or PGE2 (1 microgram/kg) were injected into the jugular vein of the donor dog, there was a slight fall in blood pressure (5-10 mm Hg) and a slight degree of tachycardia (2-6 beats/min). However, larger doses of PGI2 (1-10 microgram/kg) or PGE2 (3-10 microgram/kg) produced hypotension that was associated with marked bradycardia. The bradycardia produced by both PGE2 and PGI2 in the donor dog was blocked by either atropine pretreatment or vagotomy and was inverted to tachycardia. The tachycardia was significantly suppressed by propranolol. Administration of PGI2 either to the donor dog or directly into the sinus node arterial cannula did not alter the atrial rate or developed tension in the isolated blood perfused atrial preparation. In contrast, when PGE2 was given in larger doses (10 microgram/kg) to the donor dog, the sinus rate and developed tension in the isolated atria were increased. This effect was markedly diminished after propranolol treatment. Administration of PGE2 (1-30 microgram) close-arterially into the sinus node artery produced positive chronotropic and inotropic effect which was not statistically significant. We conclude that PGI2 and PGE2 produce a negative chronotropic effect which is due to increased vagal activity and that these agents have no direct cardiac stimulatory effects in the anesthetized dog.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004347:Drug Interactions; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology*; D014628:Vagotomy
D011453:Prostaglandins; D011458:Prostaglandins E; D001285:Atropine; D011433:Propranolol; D011464:Epoprostenol; D007545:Isoproterenol; D009638:Norepinephrine