Role of cyclooxygenase metabolites in mediating platelet-induced baroreceptor dysfunction. Li, Zhi, Xin Su, and Mark W. Chapleau. The Department of Internal Medicine and The Cardiovascular, Center, University of Iowa College of Medicine and The Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242
APStracts 2:0124H, 1995.
The goal of the study was to determine the role of cyclooxygenase metabolites in mediating platelet-induced suppression of baroreceptor activity. Baroreceptor activity was recorded from the isolated carotid sinus in anesthetized rabbits. Intraluminal exposure of the carotid sinus to washed rabbit platelets resuspended in Krebs buffer (3x108 cells/ml) and activated with thrombin significantly decreased baroreceptor activity recorded from the whole carotid sinus nerve with maximum activity decreasing to 87+5% of the control maximum (p<0.05, n=5). Inhibition of cyclooxygenase with indomethacin reduced basal carotid sinus prostacyclin (PGI2) formation and decreased maximum baroreceptor activity to 84+2% of control (p<0.05, n=8). After treatment of platelets and carotid sinus with indomethacin, platelets alone which failed to influence nerve activity before indomethacin, now decreased maximum activity to 55+7% of control and decreased the slope of the pressure-activity relation (gain) from 1.19+0.06 to 0.62+0.08 %/mmHg (p<0.05, n=8). The suppression of baroreceptor activity was even greater during exposure to thrombin-activated platelets after indomethacin (n=4). Activated platelets also decreased significantly the activity recorded from single baroreceptor fibers (n=3) and decreased carotid diameter to an equivalent extent before and after indomethacin. The platelet-induced suppression of activity was neither attenuated nor enhanced after the selective thromboxane (TXA2) synthesis inhibitor and receptor blocker CGS 22652. The stable TXA2/endoperoxide mimetic U46619 caused similar vasoconstriction as platelets but did not influence baroreceptor gain or maximum activity. The results indicate: 1) Rabbit platelets aggregating in carotid sinus cause vasoconstriction and decrease baroreceptor sensitivity; 2) The suppression of baroreceptor activity cannot be fully explained by the vasoconstriction; and 3) TXA2 from platelets does not mediate, and PGI2 or other prostanoids oppose the platelet-induced suppression of activity. Impaired formation of PGI2 and platelet activation may cause baroreceptor dysfunction in atherosclerotic and thrombotic states. 

Received 27 April 1994; accepted in final form 28 February 1995.
APS Manuscript Number H359-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 April 1995.