Adenosine-induced coronary release of prostacyclin at normal and low pH in isolated heart of rabbit.
Rabbit hearts were perfused by the Langendorff method with drug-free perfusion medium or with a medium containing adenosine (10(-7) M-10(-4)M) and the coronary and transmyocardial efflux rates of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were measured. Perfusion was performed both at pH 7.4 and 6.9. In other experiments the hearts were pre-labelled with [14C]-arachidonic acid and the coronary efflux of radioactivity and of labelled lipids and 6-keto-PGF1 alpha were determined. The basal coronary flow was elevated by almost 70% during tissue acidosis, in comparison to control. Adenosine induced a dose-dependent increase in the coronary flow, amounting to about 75% at normal pH and a drug concentration of 10(-5)M. The adenosine-induced increase in coronary flow was not facilitated by low pH. The base coronary efflux of 6-keto-PGF1 alpha from the hearts was 2.5--3.6 ng min-1. Adenosine (10(-6)-10(-5)M) significantly facilitated this efflux, up to 6.5 ng min-1. The efflux of 6-keto-PGF1 alpha was not changed by perfusion with acidic medium, either in the basal state or during perfusion with adenosine. The basal interstitial efflux of 6-keto-PGF1 alpha was 4.5-5.5 ng 3 min-1. This efflux was not affected by perfusion of the heart with adenosine-containing medium. In hearts pre-labelled with [14C]-arachidonic acid, adenosine (10 microM) induced a specific liberation of labelled lipid-extractable substances, including 6-keto-PGF1 alpha. 6 From these data we conclude that adenosine stimulates the liberation of 6-keto-PGFI. from the rabbit heart by increasing precursor availability and subsequent formation of prostacyclin in the coronary vessels. Furthermore, the increase in coronary flow induced by tissue acidosis is not related to an augmented formation of prostacyclin.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism*; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D011817:Rabbits
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D000241:Adenosine