Prostacyclin-induced coronary vasodilation. Interactions with adenosine, cyclic AMP and energy charge in the rat heart in vitro.
The action of prostacyclin (PGI2) on several biochemical and physiological parameters of myocardial function and coronary perfusion was studied in the rat heart in vitro, perfused according to Langendorff either at constant pressure (65 mmm Hg) or at constant volume (8 ml/min). PGI2 dose-dependently decreased coronary vascular resistance, the ED50, being 5--10 nM, whereas that of adenosine was 550--650 nM. PGI2 (30 nM) did not alter the myocardial energy-rich phosphate content but diminished myocardial cAMP by 23% and adenosine release by 61%. In contrast to adenosine, the coronary dilating activity of PGI2 was not inhibited by isobutyl-methyl-xanthine (MIX; 0.4 microM). There were no direct effects of PGI2 on myocardial contractile force, oxygen consumption or heart rate. The results provide evidence for (1) a direct powerful coronary dilating activity of PGI2 which appears to be independent of adenosine, (2) the absence of any direct activity of the compound on myocardial contraction and energy charge.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D000242:Cyclic AMP / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004734:Energy Metabolism / Q000187:drug effects; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D009206:Myocardium / Q000032:analysis / Q000378:metabolism; D010710:Phosphates / Q000032:analysis; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D010710:Phosphates; D011453:Prostaglandins; D014665:Vasodilator Agents; D011464:Epoprostenol; D000242:Cyclic AMP; D000241:Adenosine; D015056:1-Methyl-3-isobutylxanthine