Interactions between nitric oxide and prostacyclin in myocardial ischemia and endothelial cell cultures.
This study investigates biochemical and functional interactions between NO and PGI2 that generate pathways in two different in vitro assays: porcine aortic endothelial cells (PAEC) and reperfused ischemic Langendorff hearts of rabbits. Using cGMP as an index of NO generation and 6-oxo-PGF1 alpha as an index for PGI2 production in endothelial cells, it is demonstrated that the two metabolic pathways for NO and prostacyclin formation act independent of each other. Moreover, NO appears to have an autocrine function in endothelial cells which does not exist with PGI2, probably because of a lack of PGI2 receptors. Endothelial damage in the course of myocardial ischemia is associated with a marked increase in mediator release whose inhibition has consequences for both myocardial and coronary function: inhibition of NO formation also inhibits PGI2 release and the recovery of coronary vessel tone with only minor if any effect on myocardial contractility. In contrast, inhibition of PGI2-generation results in marked deterioration of myocardial recovery with only minor changes in coronary perfusion. It is concluded from these data that PGI2 in endothelial injury is important for preservation of myocardial function while NO might mainly be involved in control of local vessel tone.
Schrör
K
K
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, FRG.
Woditsch
I
I
Strobach
H
H
Schröder
H
H
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000032:analysis; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism* / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D015425:Myocardial Reperfusion; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D011817:Rabbits; D013552:Swine
D009569:Nitric Oxide; D000001:Calcimycin; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D000242:Cyclic AMP; D006152:Cyclic GMP