Influence of endothelium-derived relaxing factor on platelet function and hemostasis in vivo.
Endothelium-derived relaxing factor (EDRF) is a potent vasodilator, and is also, in vitro, a platelet-inhibitor. Experiments were performed to determine whether systemically released EDRF inhibits platelet-dependent hemostasis in vivo. Rabbits were treated with agents to release or block EDRF, and 5 standardized incisions were made in the ear. Carbachol, infused to stimulate EDRF release, abruptly lowered the blood pressure and caused increased bleeding. Neither effect was attributable to prostacyclin since neither was blocked by treatment of the rabbits with acetylsalicylic acid. In contrast, both the hypotension and bleeding were attenuated by the selective antagonist of EDRF synthesis, NG-nitro-L-arginine. However, neither the hypotension nor the bleeding associated with carbachol was inhibited by an infusion of free hemoglobin, used to scavenge intraluminally-released EDRF. We conclude that in this model endogenously-released EDRF increases bleeding indirectly by provoking vasodilatation, rather than directly by inhibiting platelet function.
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
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DS
Houston
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Buchanan
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D006454:Hemoglobins / Q000494:pharmacology; D006470:Hemorrhage / Q000139:chemically induced / Q000503:physiopathology; D006487:Hemostasis / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D019335:Nitroarginine; D011817:Rabbits; D013223:Statistics as Topic
D006454:Hemoglobins; D019335:Nitroarginine; D009569:Nitric Oxide; D002217:Carbachol; D001120:Arginine