Effect of atherosclerosis on responses of the perfused rabbit carotid artery to human platelets.
Vascular responses to intraluminal and abluminal activation of human platelets were examined in carotid arteries from normal and atherosclerotic rabbits. The carotid artery was perfused in vitro, platelets were activated with thrombin (0.1 unit/ml), and changes in diameter were measured. In vessels from normal animals, intraluminal activation of platelets produced dilatation of preconstricted arteries. The dilator response was attenuated by N omega-nitro-L-arginine (10(-5) M), an inhibitor of synthesis of endothelium-derived relaxing factor-nitric oxide (EDRF-NO), and augmented by LY53,857 (10(-5) M), a 5-HT2-serotonergic antagonist. Abluminal activation of platelets produced modest constriction in quiescent arteries, which was inhibited by LY53,857. Intraluminal but not abluminal ADP produced pronounced dilatation of preconstricted arteries. In vessels from atherosclerotic animals, endothelium-dependent dilatation to intraluminal activation of platelets and to ADP was impaired and dilator responses to sodium nitroprusside were normal. These experiments indicate that 1) intraluminal activation of human platelets produces endothelium-dependent dilatation in perfused carotid arteries, whereas abluminal activation of human platelets produces vasoconstriction, which is mediated primarily by serotonin, and 2) atherosclerosis markedly impairs vasodilator responses to activation of human platelets, probably because vasodilatation to ADP released from platelets is impaired.
Kaul
S
S
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Padgett
R C
RC
Waack
B J
BJ
Brooks
R M
RM
Heistad
D D
DD
D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology*; D001792:Blood Platelets; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology
D009599:Nitroprusside; D012701:Serotonin; D000244:Adenosine Diphosphate; D000109:Acetylcholine