title: Platelet activation in carotid sinuses triggers reflex sympathoinhibition and hypotension.
abstract: The carotid sinuses, one of the major sites of baroreceptor innervation, are also a common site of atherosclerotic lesions and platelet aggregation. The goal of the present study was to determine whether platelet activation in carotid sinuses causes reflex-mediated changes in renal sympathetic nerve activity and arterial pressure. Rabbit platelets were isolated, resuspended in Krebs' buffer, and activated by thrombin. Injection of activated platelets (3 x 10(8) platelets/mL) into the vascularly isolated carotid sinuses of anesthetized rabbits essentially eliminated sympathetic nerve activity and acutely decreased mean arterial pressure from 126 +/- 5 to 53 +/- 4 mm Hg (n=16; P < .05). Sympathetic activity and arterial pressure returned to control levels over a period of minutes despite sustained exposure to activated platelets. Injection of U-46619, a thromboxane analogue and vasoconstrictor, into carotid sinuses did not alter sympathetic activity or arterial pressure. However, serotonin (5-hydroxytryptamine [5-HT]), which is known to be released from activated platelets, and the 5-HT3 receptor agonist phenylbiguanide mimicked the effect of platelets. Furthermore, the platelet-induced reflex inhibition of sympathetic activity and hypotension were not altered by the cyclooxygenase inhibitor indomethacin but were attenuated significantly by 5-HT receptor antagonists. Platelet activation inhibited sympathetic activity to 5 +/- 2% of control in the absence of antagonists but to only 35 +/- 11 and 76 +/- 4% of control after selective blockade of 5-HT2 and 5-HT3 receptors with ketanserin and MDL-72222, respectively. The results indicate that (1) platelet activation in carotid sinuses triggers reflex inhibition of sympathetic nerve activity and hypotension; (2) the reflex is not caused by carotid vasoconstriction and is not mediated by prostanoids; and (3) the reflex is mediated by 5-HT acting primarily on 5-HT3 and to a lesser extent on 5-HT2 receptors. We speculate that this reflex may contribute to arterial pressure lability and susceptibility to stroke in patients with carotid atherosclerotic disease.
authors.affiliation: Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: H Z
authors.initials: HZ
authors.lastname: Mao
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: M W
authors.initials: MW
authors.lastname: Chapleau
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002346:Carotid Sinus / Q000503:physiopathology*; D005260:Female; D006973:Hypertension / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D015539:Platelet Activation; D011817:Rabbits; D012018:Reflex; D013564:Sympathetic Nervous System / Q000503:physiopathology*