Regulation of glycolytic flux by coronary flow in guinea pig heart. Role of vascular endothelial cell glycocalyx.
Hemodynamic forces continuously act on endothelial cell lining of blood vessels. Blood flow, perfusing pressure, and shear stress are known to induce the release of bioactive substances from the endothelium. Furthermore, coronary flow (CF) is a well-known stimulant of myocardial contraction. Our concern was whether other Ca(2+)-dependent responses like glycolytic flux (Gf) were also CF dependent. For this purpose, isolated guinea pig hearts were perfused with a medium containing 5 mM 3-[3H]glucose, and the 3H2O released during perfusion was measured as an index of Gf. Changes in CF within the 3- to 25-ml/min range resulted in linear increase of Gf. This stimulatory effect of CF was also observed in K(+)-arrested hearts. In addition, increasing shear stress on addition of dextran to the perfusing solution (5% and 10% wt/vol), while keeping CF constant, also stimulated Gf. We hypothesized that endothelial cell membrane glycocalyx may act as sensor to this stimuli. Thus one would expect that substances acting on these structures (enzymes heparinase, hyaluronidase, or chondroitinase or the lectin concanavalin A) when added to the perfusate might inhibit the CF-induced Gf. The results showed that concanavalin A and heparinase inhibited the Gf-CF-induced response, whereas chondroitinase and hyaluronidase had no effect. These findings suggest that there may be a selective effect of these agents affecting the Gf response to CF. Our data suggest that CF stimulates Gf through shearing forces acting on specific endothelial glycocalyx component(s). Therefore, deformation of these components could result in the transduction of physical signals into release of chemical messengers that act on the biochemical machinery of underlining parenchymal cells.
Suárez
J
J
Department of Physiology, University of Virginia Health Sciences Center, Charlottesville 22908.
Rubio
R
R
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology*; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D008297:Male; D011134:Polysaccharides / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D013314:Stress, Mechanical
D006023:Glycoproteins; D011134:Polysaccharides; D000241:Adenosine; D011188:Potassium