Vascular Endothelial Cell-Cardiac Myocyte Crosstalk in Achieving a Balance between Energy Supply and Energy use

Abstract

In isolated perfused hearts, endothelial cells in the coronary arterial vascular system release substances that can alter the contractility of the cardiac myocytes. There are at least two different substances, one that increases and another that decreases the contractility of cardiac myocytes. The rate of release of these endothelial-derived cardioactive substances depends on the oxygen tension in the immediate vicinity of the cardiac myocytes. As the local oxygen tension increases the contractility changes in the same direction. The oxygen sensor in this regulatory system is the cardiac myocyte, which then releases substances that regulate the secretion of endothelin and a relaxant by endothelial cells. The result is a loop involving cross talk between coronary endothelial cells and cardiac myocytes to modulate cardiac contractility in accordance with the oxygen supply to the cardiac myocytes. Preliminary data suggest that the change in contractility is related to a change in structure and position of the cross bridge due to phosphorylation of a protein in the thick filament.

In performing the function of pumping blood according to the needs of the organism, the heart must maintain a balance between its energy supply and the rate at which it uses energy. Cardiac myocytes cannot sustain an oxygen debt or call upon a large store of immediately available energy. There are basically only three ways in which this balance can be achieved: variation in coronary blood flow, cardiac power and/or the efficiency of conversion of biochemical energy to hydrodynamic work. Until relatively recently, the major component in the maintenance of this balance was assumed to be variation of coronary blood flow from changes in vasomotor tone in response to alteration in pO₂, pH and pCO₂. The situation is actually more complex.

Two sets of observation have led to a greater recognition of the sophistication and refinement of the mechanisms for matching blood flow to energy utilization. Brutsaert and co-workers (1) demonstrated that removal of endocardial endothelium from isolated myocardium altered the contractility of the myocardium. Shah and co-workers (2) then demonstrated that cultured endothelial cells from the heart released substances that could change myocardial contractility. At the same time, we observed that the actomyosin ATPase activity in myocardial tissue was not always uniform, but showed a non-uniformity related to the proximity of the specific cardiac myocyte to arterial blood vessels (3). The presence or absence of perfusion of the blood vessels also made a major difference. In isolated hearts in which only 30 seconds are injured to reestablished perfusion of the blood vessels after dissection; the ATPase activity of actomyosin was uniform throughout the ventricles. In isolated cardiac trabeculae where superfusion rather than perfusion is employed, ATPase activity is not uniform (Fig. 1). The variability among the myocytes was related to their distance from the surface of the trabecula and the distance from the unperfused arterial vessels. Contrary to what had been expected, the distribution of levels of ATPase activity did not follow the gradient of oxygen tension. The most superficial myocytes had the lowest ATPase activity. This distribution of ATPase activities could be reproduced by a model in which cardioactive substances, both enhancer and inhibitor of contractility, were released by endothelial cells in blood vessels and in the endocardium according to local oxygen tension and shear stress on the blood vessels wall (4,5).