Coronary flow-induced inotropism is modulated by binding of dextrans to the endothelial luminal surface.
In isolated perfused guinea pig hearts, coronary flow causes a positive inotropic effect [positive coronary flow-induced effect (+CFIE)] that could be altered by dextrans (Dx) in the coronary perfusion solution. To test this possibility, Dx of 20, 40, 70, and 500 kDa were infused and found to modulate +CFIE; however, when Dx infusion was terminated, the effect persisted, i.e., was irreversible/nonwashable, suggesting that Dx may bind to luminal endothelial lectinic structures. This hypothesis was tested when Dx [with fluorescent traces (D*)] bound to the vessel wall was hydrolyzed by dextranase infusion and washout of D* fragments completely reverted the +CFIE, and it was found that bound D* to be displaced by free Dx required concentrations 50-100 times that used during binding. In addition, dose-response curves for Dx on +CFIE show that the higher the Dx molecular mass, the lesser the concentration required to have an effect. Because a large Dx molecule has a greater number polymeric glucose branches, it can bind to a larger number of endothelial lectinic sites, requiring a lower concentration to affect +CFIE. Our results suggest that luminal endothelial lectinic structures are part of the flow-sensing assembly.
Gonzalez-Castillo
Carmen
C
Facultad de Medicina, Departomento de Fisiologia y Farmacologia, Universidad Autonona de San Luis Potosi, San Luis Potosi, San Luis Potosi CP 78210 Mexico.
Rubio
Rafael
R
Zenteno-Savin
Tania
T
D000418:Albumins / Q000008:administration & dosage / Q000378:metabolism; D000818:Animals; D001783:Blood Flow Velocity; D003326:Coronary Circulation; D003911:Dextrans / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D008970:Molecular Weight; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D012996:Solutions; D013268:Stimulation, Chemical; D014783:Viscosity
D000418:Albumins; D003911:Dextrans; D005456:Fluorescent Dyes; D012996:Solutions; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate