Endogenous endothelium-derived relaxing factor inhibits platelet adhesion under whole blood flow conditions ex vivo

In this study, we used carbachol to stimulate the endogenous endothelium-derived relaxing factor (EDRF) release in male Sprague-Dawley rats. One ml of native blood was drawn from the femoral artery and directly passed through a parallel-plate flow chamber. This system allowed us to examine ex vivo platelet adhesion to fibrinogen-coated surface under whole blood flow conditions. Our results demonstrated that 1) the intravenous administration of carbachol induced a transient decrease of blood pressure, reduction in platelet adhesion ex vivo, and elevation in platelet cGMP level; 2) coadministration of carbachol with hemoglobin, a scavenger of EDRF, inhibited these carbachol effects; 3) the administration of hemoglobin or N omega-nitro-L-arginine, an inhibitor blocking the NO synthesis pathway, caused elevated blood pressure in vivo, increased platelet adhesion ex vivo, and decreased cGMP content in platelets. We conclude that endogenous EDRF not only modulates vascular tone, but also influences platelet adhesion under flow conditions.