AJP - Heart and Circulatory Physiology, Vol 269, Issue 2 599-H608, Copyright © 1995 by American Physiological Society
Role of cyclooxygenase metabolites in mediating platelet-induced baroreceptor dysfunction
Z. Li, X. Su and M. W. Chapleau
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
The goal of the study was to determine the role of cyclooxygenase
metabolites in mediating platelet-induced suppression of baroreceptor
activity. Exposure of the isolated carotid sinus of rabbits to
thrombin-activated rabbit platelets (3 x 10(8) cells/ml Krebs buffer)
decreased baroreceptor activity (P < 0.05) without significantly
altering the slope of the pressure-activity relation (gain). The
platelet-induced suppression of activity was not blocked but instead was
even more pronounced after inhibition of cyclooxygenase with indomethacin;
both maximum baroreceptor activity and gain were decreased markedly. The
exacerbation of platelet-induced baroreceptor dysfunction contrasted with
equivalent carotid vasoconstrictor responses to platelets before and after
indomethacin. Furthermore, the stable thromboxane (TxA2) mimetic U-46619
caused similar vasoconstriction as platelets but did not influence
baroreceptor gain or maximum activity. In contrast to indomethacin, the
selective TxA2 synthesis inhibitor and receptor blocker CGS-22652 failed to
influence platelet-induced suppression of activity. In summary, 1) rabbit
platelet aggregating in carotid sinus suppress baroreceptor activity, which
cannot be explained by the vasoconstriction, and 2) the suppression of
activity is not mediated by TxA2 from platelets and is opposed by
prostacyclin (PGI2) or other prostanoids produced in carotid sinus. The
combination of impaired formation of PGI2 and platelet activation in
atherosclerotic and thrombotic states may lead to profound baroreceptor
dysfunction.
