Vascular responses to platelet activation in normal and atherosclerotic primates in vivo.
Platelets release vasoactive substances that may contribute to augmented vasoconstriction. In this study, we examined vascular responses to activation of platelets in vivo by infusion of collagen. Purified bovine collagen was infused into the blood-perfused hind limb of normal and atherosclerotic cynomolgus monkeys. Resistance of the total limb and large arteries was measured at constant flow. In normal monkeys, collagen produced a decrease in total limb resistance, with a modest constrictor response of the large arteries. In atherosclerotic monkeys, collagen produced a transient, small decrease in total limb resistance, with pronounced constriction of large arteries. Indomethacin (5 mg/kg i.v.) and the thromboxane A2/prostaglandin H2 receptor antagonist SQ29,548 (2 mg/kg i.v.) virtually abolished the large-artery constrictor response to collagen in atherosclerotic monkeys. The 5-HT2-serotonergic receptor antagonist ketanserin (0.6 mg/kg i.v.) had no effect on the vasoconstrictor response. We conclude that 1) large arteries constrict and small vessels dilate in response to collagen-mediated activation of platelets in vivo in normal and atherosclerotic monkeys, 2) large-artery constriction in response to activation of platelets is augmented in atherosclerotic monkeys, and 3) the augmented large-artery constriction in atherosclerotic monkeys may be mediated primarily by thromboxane. The findings provide evidence that platelets may contribute to augmented constrictor responses of atherosclerotic arteries.
Department of Internal Medicine, Veterans Affairs Medical Center, Iowa City, Iowa.
S
S
Kaul
D D
DD
Heistad
A
A
Mügge
M L
ML
Armstrong
D J
DJ
Piegors
J A
JA
Lopez
D000241:Adenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000503:physiopathology*; D001808:Blood Vessels / Q000503:physiopathology*; D003094:Collagen / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006439:Hemodynamics; D008055:Lipids / Q000097:blood; D008297:Male; D015539:Platelet Activation / Q000502:physiology*; D011323:Primates; D012016:Reference Values; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation
D008055:Lipids; D000244:Adenosine Diphosphate; D003094:Collagen; D000241:Adenosine