THE ENDOCARDIAL ENDOTHELIAL Na +!IC ATPase AND CARDIAC CONTRACTION Paul Fransen, Jan Hendrickx, and Gilles De Keulenaer* 1. INTRODUCTION The cavitary sides of the ventricles are covered by the endoC81dium, which consists of an innenuost thin layer of endothelial cells (1-3 I'm, the endocmdial endothelium, EE) and a subjacent layer of interstitial tissue. Although the EE was initially considered as a passive monolayer of cells at the bonier between the ciICUlating blood and the underlying caniiomyocytes, current insights now suggest an obligatoI)' role of the EE in the regulation of normal caniiac function (for review, see Brutsaert, 2003). Since Brutsaert and co-workers in 1988 for the first time showed that selective removal of the EE layer from the myocaniium in papillary muscles from cat hearts altered mechanical peIfonuance of the muscle, this obseIVation was continued in caniiac muscle preparations from different species (Smith et al., 1991, Wang and Morgan, 1992) and also in the inta;:t animal in-vivo (Gillebert et al., 1992; De Hert et al., 1993). Coronary endothelial cells have been described to have similar inotropic activity (Li et al., 1993). How the presence of an endothelial monolayer covering a thick layer of caniiomyocytes influences the mechanical peIfonnance of these myocytes, is presently under investigation. In their initial paper, B rutsaert et al. (1988) sta1ed: "As for the mechanisms involved ... , we can only speculate at present. We might think of at least three possible ways by which the endocaniium could affect myocaniial peIfonnance: by the release of a chemical substance or messenger, by an electrochemical barrier, or by both." Today, we know that EE cells respond to humoral and mechanical stimuli by releasing biologically active substances, which modulate myocaniial controctility (stimulus-secretion-contraction coupling) (Figure 1). This cross-talk mechanism between endothelium and muscle cells has been extensively studied in blood vessels, especially following the obseIVation of Furchgott and Zawadski (1980) /bout the obligatoI)' role of the vascular endothelium in acetylcholine-induced vasorelaxation. Bioassay studies demonstrated that endothelial cells released a labile, difIusable non-prostanoid factor identified as nitric oxide (Rubanyi and Vanhoutte, 1986; Furchgott and Vanhoutte, 1989). Paul Fransen, Jan Hendrickx and Gilles De Keulenaer, Department ofPhannacology, University of Antwerp, Groenenborgerlaan, 171, B·2020 Antwerpen, Belgium. E-mail: paul.fransen@ua.ac.be Molecular and Cellular Aspects of Muscle Contraction Edited by H. Sugi, Kluwer Academic/Plenum Publishers, 2003 43