Cardiovascular responses to PGI2 (prostacyclin) in the dog.
Arachidonic acid (AA) produces characteristic hemodynamic changes in the canine circulation. These responses are blocked by prostaglandin (PG) synthetase inhibitors, indicating that AA and its nonprostanoic metabolites are not vasoactive. The hemodynamic effects of the cyclic endoperoxides, thromboxanes, and PGD2, PG2, and PGF2a differ from those produced by AA. PGI2, a newly identified product of AA, is reported to relax arterial strips. However, its cardiac and systemic effects are unknown. In 12 open-chest, anesthetized dogs, PGI2 (0.25-5.0 microgram/kg) produced a dose-related decrease in systemic arterial pressure (BP) and myocardial contractile force (MCF). In five left ventricular bypass preparations, PGI2 produced only a slight decrease in MCF at all doses, whereas the BP decreases were parallel to those in the intact preparation. AA, PGD2, PGE2, and PGI2 were administered in random order by bolus intravenous injections in approximately equidepressor doses to intact dogs. BP fell with each agent (AA, 300 microgram/kg, -25 percent; PGD2, 5 microgram/kg, -26 percent; PGE2, 5 microgram/kg, -26 percent PGI2, 0.5 microgram/kg, -26 percent). The vasodepressor action of PGI2 was approximately 10 times greater than that of PGD2 and PGE2. Pulmonary arterial pressure (PAP) rose significantly with PGD2 and PGE2 (AA, -1 percent; PGD2 +66 percent; PGE2, +20 percent; PGI2, -1 percent). Only PGE2 had a significant effect on MCF (AA, +7 percent; PGD2, +5 percent, PGE2, +20 percent; PGI2, -0.3). At this dose, PGI2 resembles AA in that it has little effect on either PAP or MCF. Of all known AA metabolites the response to PGI2 most closely resembles that of exogenous AA in the dog.
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology
D001095:Arachidonic Acids; D011453:Prostaglandins; D011458:Prostaglandins E; D011464:Epoprostenol