AJP - Heart and Circulatory Physiology, Vol 252, Issue 4 743-H748, Copyright © 1987 by American Physiological Society
Thromboxane does not mediate pulmonary vascular response to monocrotaline pyrrole
P. E. Ganey and R. A. Roth
The possible involvement of thromboxane (Tx) in the pulmonary hypertension
caused by monocrotaline pyrrole (MCTP) administration to rats was
investigated by pharmacological intervention of Tx synthesis and action.
The cyclooxygenase inhibitor, ibuprofen, at doses that inhibited platelet
function and suppressed plasma Tx levels, did not attenuate MCTP-induced
right ventricular hypertrophy or increased lung weight. Dazmegrel, an
inhibitor of Tx synthetase, did not affect the MCTP-induced increase in
lung weight or the elevation of lactate dehydrogenase activity or protein
concentration in bronchopulmonary lavage fluid, despite significant
reduction of the plasma concentration of Tx. Dazmegrel also did not alter
the vascular leak or right ventricular hypertrophy due to administration of
MCTP to rats. Finally, the Tx receptor antagonist L-640,035 was tested
using a dosing regimen that reduced the increase in right ventricular
pressure caused by a stable endoperoxide analogue in MCTP-treated rats.
Cotreatment with L-640,035 did not attenuate the increase in lung weight,
lavage fluid lactate dehydrogenase activity or protein concentration, or
the pulmonary hypertension caused by MCTP. These results indicate that
interference with Tx synthesis or action does not attenuate the toxic
effects of MCTP and suggest that Tx is not necessary for the
cardiopulmonary response to MCTP.
