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.