AJP - Heart and Circulatory Physiology, Vol 251, Issue 4 808-H814, Copyright © 1986 by American Physiological Society
Prostanoid mediation of pulmonary vascular response to acetylcholine in rabbits
H. A. el Kashef and J. D. Catravas
We studied the effects of acetylcholine (ACh) in the anesthetized,
open-chest rabbit. ACh (5-20 nmol/kg), administered as a bolus into the
right jugular vein, produced a dose-dependent increase in both pulmonary
arterial pressure and pulmonary vascular resistance but a decrease in
systemic arterial pressure and pulmonary blood flow. All these effects were
prevented by atropine. Pretreatment with the phospholipase A2 inhibitor
quinacrine reduced the pulmonary vascular responses to ACh without
affecting systemic arterial pressure. Similarly, treatment with the
cyclooxygenase inhibitors indomethacin or meclofenamate completely
eliminated the pulmonary vascular response to ACh without affecting
systemic arterial pressure or pulmonary blood flow. Treatment with the
lipoxygenase inhibitor nordihydroguaiaretic acid, however, had no effect on
the pulmonary or systemic vascular responses to ACh. Furthermore,
administration of the thromboxane A2 synthetase inhibitor
7-(1-imidazolyl)-heptanoic acid or the thromboxane A2 receptor antagonist
SQ 29,548 completely eliminated the pulmonary vascular responses to ACh
without affecting systemic arterial pressure or pulmonary blood flow.
Plasma levels of immunoreactive thromboxane B2 increased after ACh, in the
absence but not in the presence of the thromboxane A2 synthetase inhibitor.
The results of the present study indicate that in the rabbit ACh has
opposite actions in the systemic (dilatory) versus pulmonary (constrictor)
circulation, arachidonic acid metabolites mediate the pulmonary but not the
systemic vascular response to ACh, and thromboxane A2 appears to mediate
the pulmonary vasoconstrictor response to ACh.
