Prostacyclin rather than endogenous nitric oxide is a tissue protective factor in myocardial ischemia.
Nitric oxide (NO) and prostacyclin (PGI2) were determined in effluents of Langendorff-perfused rabbit hearts subjected to 2 h of global low-flow ischemia and subsequent reperfusion. PGI2 release [6-oxo-prostaglandin (PG) F1 alpha] was significantly enhanced during early reperfusion and remained elevated. NO formation was reduced during ischemia but did increase substantially during reperfusion. Indomethacin (3 microM) significantly suppressed ischemia-related 6-oxo-PGF1 alpha and NO release. This was accompanied by severely diminished myocardial recovery. NG-nitro-L-arginine (L-NNA) (100 microM) suppressed NO generation without major effects on 6-oxo-PGF1 alpha generation and cardiac dysfunction but with a remarkable increase in coronary perfusion pressure. These effects of L-NNA were antagonized by L-arginine, whereas the effects of indomethacin were not. There was a substantial loss of creatine kinase specific activity from reperfused ischemic hearts, which was further aggravated by indomethacin but not by L-NNA. These data demonstrate a cardioprotective and endothelium-protective role of PGI2 in myocardial ischemia, which also involves preservation of NO generation. Endogenous NO appears to be important for local regulation of coronary flow.
Woditsch
I
I
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany.
Schrör
K
K
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003326:Coronary Circulation; D003327:Coronary Disease / Q000473:pathology / Q000503:physiopathology*; D003402:Creatine Kinase / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism / Q000502:physiology*; D006321:Heart / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D012016:Reference Values
D009569:Nitric Oxide; D001120:Arginine; D011464:Epoprostenol; D003402:Creatine Kinase; D007213:Indomethacin