Ca2+-independent inhibition of myocardial contraction by coronary effluent of hypoxic rat hearts

Endothelial cells release agents that influence cardiac contraction. We recently reported that cultured hypoxic endothelial cells release an unidentified factor(s) that inhibits myocardial contraction. In this study, we investigated the effects of coronary effluent of isolated hypoxic rat hearts on isolated rat ventricular myocyte contraction. Coronary effluent collected during brief moderate hypoxia significantly depressed myocyte twitch shortening and decreased diastolic length, with only minor reduction in intracellular Ca2+ transients. These effects were similar to those of hypoxic rat coronary microvascular endothelial cell superfusates and were reversed by reoxygenation of hearts. "Hypoxic" coronary effluent exerted essentially Ca2+-independent effects on myofilament interaction in intact myocytes, as assessed by 1) peak Ca2+-shortening relations, 2) phase-plane analysis of instantaneous Ca2+-cell length relations, and 3) "steady-state" myofilament responses in tetanized, sarcoplasmic reticulum-disabled cells. Thus an unidentified substance(s) that inhibits myocyte shortening predominantly via effects on the myofilaments is reversibly released during acute moderate hypoxia of isolated hearts, presumably from coronary endothelial cells. Release of such an agent may be relevant to the cardiac contractile response to hypoxia.