MYOCARDIAL ADENOSINE STIMULATES RELEASE OF CYCLIC ADENOSINE-MONOPHOSPHATE FROM CAPILLARY ENDOTHELIAL-CELLS IN GUINEA-PIG HEART

Activation of coronary endothelial cell adenylate cyclase was studied in the isolated guinea pig heart by prelabelling endothelial adenine n ucleotides using intracoronary infusion of [H-3]-adenosine, and measur ing the coronary efflux of [H-3]-cyclic adenosine monophosphate (cAMP) . Hypoxia (30 % O2) caused a 4-fold increase in coronary release of [H -3]-cAMP, which was decreased by 63 % by infusion of the adenosine rec eptor antagonist, theophylline (50 muM). During normoxic control condi tions, degrading adenosine to non-vasoactive inosine by intracoronary infusion of adenosine deaminase (1.7 U/ml) caused a 20 % decrease in t he release of [H-3]-cAMP. The effect of adenosine deaminase was revers ed by a specific enzyme inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride. Coronary efflux of [H-3]-cAMP during intracoronary inf usion of 1 muM adenosine triphosphate (ATP), adenosine diphosphate or adenosine monophosphate (AMP) (plus adenosine deaminase 8 U/ml) was on ly 13 % of that due to 1 muM adenosine. Adenosine receptor blockers th eophylline and CGS 15943A caused equivalent inhibition of the coronary vasodilator actions of adenosine and ATP. Intracoronary infusion of p rostaglandin E1 and the beta2-adrenergic agonist procaterol caused par allel, dose-dependent increases in coronary conductance and the venous release of [H-3]-cAMP. It is concluded that (1) under both normoxic a nd hypoxic conditions, adenosine formed by the heart may activate endo thelial cell adenylate cyclase via membrane adenosine receptors, (2) c oronary receptors for adenosine and ATP share common ligand affinities but ATP receptors are not coupled to adenylate cyclase, and (3) other vasodilators known to activate endothelial adenylate cyclase in vitro cause parallel increases in coronary conductance and adenylate cyclas e activity in the beating heart.