Contribution of prostaglandins in hypoxia-induced vasodilation in isolated rabbit hearts. Relation to adenosine and KATP channels.

Abstract

The mechanism of hypoxia-induced coronary vasodilation was studied in isolated, saline-perfused rabbit hearts under constant flow conditions. Reduction in the perfusion solution PO2 (from 520 +/- 6 to 103 +/- 9 mm Hg) under control conditions halved the coronary resistance and was accompanied by a significant release of the prostaglandin (PG) 6-keto-PGF1 alpha (from 1.8 +/- 0.3 to a maximum of 4.4 +/- 0.9 pmol min-1 g-1). The cyclooxygenase inhibitor, diclofenac (1 microM), blocked the release of PGI2 and reduced hypoxia-induced vasodilation (from 47 +/- 8% to 25 +/- 5%, P < 0.05). The relative contribution of adenosine, prostaglandins, and adenosine triphosphate (ATP)-sensitive K+ channel (KATP channel) activation in hypoxia-induced vasodilation was assessed by comparing the differential change (control response minus response after treatment) in coronary perfusion pressure (CPP) during infusion of 8-phenyltheophylline (8-PT), diclofenac, and glibenclamide, respectively. The differential change in CPP with 8-PT and diclofenac given together (-48 +/- 7%) was found to be equivalent to the sum of their respective effects (-24 +/- 7 and -19 +/- 4%, respectively). Glibenclamide (0.3 microM) reduced significantly hypoxia-induced vasodilation (differential change in CPP of -27 +/- 6%) as well as the dilator response to 10 microM adenosine and to the stable PGI2-analogue, iloprost. Forskolin-induced coronary vasodilation in arrested hearts was slightly, but significantly, reduced by glibenclamide. Our results suggest that both cyclooxygenase products and adenosine, acting independently, and concomitantly, contribute to the dilator response of coronary resistance vessels to hypoxia, in part through the activation of KATP channels.(ABSTRACT TRUNCATED AT 250 WORDS)