Role of the endothelial glycocalyx in dromotropic, inotropic, and arrythmogenic effects of coronary flow

Coronary flow regulates cardiac functions, and it has been suggested that e ndothelial membrane glycosylated proteins are the primary shear stress mech anosensors. Our hypothesis was that if these proteins are the sensors for f low, then intracoronary perfusion of lectins or specific antibodies should differentially depress coronary flow-enhanced responses of different parenc hymal cell types such as auricular-ventricular (A-V) nodal cells (dromotrop ic effect), contractile myocytes (inotropic effect), and junctional Purkinj e-muscle cells (spontaneous ventricular rhythm). The coronary flow stimulat ory effects on A-V delay and spontaneous ventricular rhythm were selectivel y depressed by six of eight lectins. None of the lectins depressed the coro nary flow inotropic effect. Antibodies against endothelial surface proteins , alpha(v)beta(5)-integrin and sialyl-Lewis(b) glycan, depressed the dromot ropic but not the inotropic effects of coronary flow, whereas the vascular cell adhesion molecule 1 antibody had no effect on the dromotropic, but enh anced the inotropic, effect. The fact that lectins and antibodies different ially depressed regional coronary flow effects suggests that there is a che mical distinctiveness in their intravascular endothelial cell surfaces. How ever, nonselective cross-linking of endothelial glycocalyx proteins with 2, 000-kDa dextranaldehyde or vitronectin indistinctively depressed the dromot ropic and inotropic effects of coronary flow. These results indicate that c oronary flow-induced stress acts on specific structures located in the capi llary intravascular membrane glycocalyx.