MYOCARDIAL PERFORMANCE IS MODULATED BY INTERACTION OF CARDIAC ENDOTHELIUM-DERIVED NITRIC-OXIDE AND PROSTAGLANDINS

Objective: The endocardial endothelium modulates the performance of the subjacent myocardium and plays an important role in regulating cardiac function. The aim of this study was to investigate the effects on cardiac function of the mutual interaction of nitric oxide (NO) and prostaglandins released from the endocardial endothelium. Methods: The effects of NO and prostaglandin interaction were investigated in isolated cat papillary muscle (Krebs Ringer; 1.25 mM Ca2+; 35 degrees C), using substance P (1 mu mol . litre(-1)) to release NO, L-nitroarginine (L-NOARG:30 mu mol . litre(-1)) to inhibit NO synthase, arachidonic acid (10 mu mol . litre(-1)) to stimulate endogenous prostaglandin (mainly prostacyclin) release, and indomethacin (1 mu mol . litre(-1)), a cyclooxygenase inhibitor. Results: Administration of substance P resulted in a negative inotropic effect. This response to substance P was abolished by arachidonic acid, while it was preserved in the presence of indomethacin. In the presence of L-NOARG, arachidonic acid induced a positive inotropic effect with prolongation of the twitch duration, while indomethacin reduced the twitch duration. Conclusions: Activation of prostaglandins abolishes the effect of NO, while prostaglandin-induced positive inotropic effect requires NO synthesis inhibition. Accordingly NO and prostaglandins interact to regulate myocardial performance.