title: Endogenous endothelium-derived relaxing factor inhibits platelet adhesion under whole blood flow conditions ex vivo.
abstract: 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.
authors.affiliation: Department of Physiology, National Cheng-Kung University Medical College, Tainan, Taiwan, Republic of China.
authors.forename: C J
authors.initials: CJ
authors.lastname: Jen
authors.forename: C T
authors.initials: CT
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001775:Blood Circulation / Q000187:drug effects / Q000502:physiology; D001792:Blood Platelets / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005340:Fibrinogen / Q000502:physiology; D006454:Hemoglobins / Q000378:metabolism; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010277:Parasympathomimetics / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019323:omega-N-Methylarginine
chemical_list: D004791:Enzyme Inhibitors; D006454:Hemoglobins; D007202:Indicators and Reagents; D010277:Parasympathomimetics; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D002217:Carbachol; D005340:Fibrinogen; D001120:Arginine; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP