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 endothelial membrane glycosylated proteins are the primary shear stress mechanosensors. Our hypothesis was that if these proteins are the sensors for flow, then intracoronary perfusion of lectins or specific antibodies should differentially depress coronary flow-enhanced responses of different parenchymal cell types such as auricular-ventricular (A-V) nodal cells (dromotropic effect), contractile myocytes (inotropic effect), and junctional Purkinje-muscle cells (spontaneous ventricular rhythm). The coronary flow stimulatory effects on A-V delay and spontaneous ventricular rhythm were selectively depressed by six of eight lectins. None of the lectins depressed the coronary flow inotropic effect. Antibodies against endothelial surface proteins, alpha(v)beta(5)-integrin and sialyl-Lewis(b) glycan, depressed the dromotropic but not the inotropic effects of coronary flow, whereas the vascular cell adhesion molecule 1 antibody had no effect on the dromotropic, but enhanced the inotropic, effect. The fact that lectins and antibodies differentially depressed regional coronary flow effects suggests that there is a chemical distinctiveness in their intravascular endothelial cell surfaces. However, nonselective cross-linking of endothelial glycocalyx proteins with 2,000-kDa dextran-aldehyde or vitronectin indistinctively depressed the dromotropic and inotropic effects of coronary flow. These results indicate that coronary flow-induced stress acts on specific structures located in the capillary intravascular membrane glycocalyx.
Rubio
R
R
Department of Physiology, University of Virginia, Charlottesville, Virginia 22903, USA. rrubio@deimos.tc.uaslp.mx
Ceballos
G
G
D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D001283:Atrioventricular Node / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003911:Dextrans / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D019276:Glycocalyx / Q000378:metabolism / Q000502:physiology*; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D037102:Lectins / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology*; D016276:Ventricular Function / Q000187:drug effects; D019096:Vitronectin / Q000494:pharmacology
D000447:Aldehydes; D000906:Antibodies; D003911:Dextrans; D037102:Lectins; D008565:Membrane Proteins; D019096:Vitronectin