Selective antagonism of the systemic vasodepressor response to PGE1 by d,1-11, 15-bisdeoxy PGE1.
Several bisdeoxy PGE1 analogs are potent, competitive antagonists of PGE1-induced colonic contractions in the gerbil. The efficacy of these analogs in antagonizing PGE1-mediated systemic vasodepression has not been previously demonstrated. In this study, serial doses of PGs were administered before, during and after infusion of d,1-11, 15-bisdeoxy PGE1. Bolus injections of PGE1 (3.0 muk/kg), PGE2 (3.0 micrograms/kg) and PGI2 (0.3 microgram/kg) were administered via the right external jugular vein to male Wistar rats. PGE1, PGE2 and PGI2 decreased systemic arterial pressure 41%, 38% and 38%, respectively. The PGE1 analog was infused (200 micrograms/kg/min) through the right common carotid artery. The analog itself had no effect on mean systemic arterial pressure, but maximum reversible inhibition (51%) of PGE1-mediated vasodepression occurred following a 50 minute infusion. No significant effect of the PGE1 analog was observed on PGE2 or PGI2-mediated vasodepression. These data demonstrate the ability to antagonize PGE1-mediated vasodepression, and to differentiate the vascular responses to PGE1 and PGE2 or PGI2.
D000527:Alprostadil / Q000031:analogs & derivatives*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D011458:Prostaglandins E / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats
D011458:Prostaglandins E; D011459:Prostaglandins E, Synthetic; C025009:11,15-bisdeoxyprostaglandin E1; D011464:Epoprostenol; D000527:Alprostadil