Effect of endothelial function on twitch configuration of the isolated myocardium from rabbits and dogs

Abstract

This series of studies were designed to evaluate 1) the myocardial contractile effect of endothelin-l; 2) whether endocardial endothelium (EE) altered the myocardial response to some inotropic agents such as endothelin; 3) whether vascular endothelium also modified the contraction of myocardium and 4) what were the changes in endocardial endothelium in pacing induced heart failure dogs. In rabbit papillary muscles, endothelin-1 produced a dose-dependent Increase in tension and a decrease in time to peak. Increasing [Ca2+]0 greatly attenuated its effects but the presence of nicardipine did not shift the dose-response curve of endothelin. EE removal from rabbit muscles did not alter the absolute changes in contractility caused by endothelin but shifted the dose-response curve to the left. Vascular endothelium dysfunction resulted in changes in papillary muscle contractile characteristics similar to that of removing EE: a shortening of twitch duration and a decrease in tension. EE removal of these muscle caused further shortening of twitch duration and a further decrease in tension. In pacing-overdrive heart failure in dogs, EE continued to modulate myocardial contractile characteristics in a fashion similar to that of normal myocardium, however, its modulating role on the myocardial contractile effects of phenylephrine was lost. This data suggests that 1) endothelin increases myocardial contractility, which is more obvious at lower [Ca2+)0; 2)EE has a modifying effect on the myocardial response to endothelin; 3) vascular endothelium aIso modulates the contractile characteristics of myocardium; 4) the modifying effects of vascular endothelium on myocardium are additive to those of EE; 5) in heart failure, the decrease in myocardial ?-1-adrenergic responsiveness that occurs Is related to EE dysfunction.