TY - JOUR
T1 - Role of the endothelial glycocalyx in dromotropic, inotropic, and arrythmogenic effects of coronary flow
AU - Rubio, Rafael
AU - Ceballos, Guillermo
PY - 2000/1
Y1 - 2000/1
N2 - 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, α(v)β5-integrin and sialyl-Lewisb 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 dextranaldehyde 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.
AB - 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, α(v)β5-integrin and sialyl-Lewisb 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 dextranaldehyde 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.
KW - Capillary perfusion
KW - Endothelial extracellular mediators
KW - Extracellular matrix molecules
KW - Glycoproteins
KW - Intravascular endothelial glycoproteins
KW - Mechanical transmission-transduction
KW - Mechanosensors
KW - Shearing forces
UR - http://www.scopus.com/inward/record.url?scp=0343114382&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.2000.278.1.h106
DO - 10.1152/ajpheart.2000.278.1.h106
M3 - Artículo
SN - 0363-6135
VL - 278
SP - H106-Hl16
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 1 47-1
ER -