ACETYLCHOLINE-INDUCED CONTRACTIONS IN ISOLATED RABBIT PULMONARY-ARTERIES - ROLE OF THROMBOXANE-A2

  • 1 February 1986
    • journal article
    • research article
    • Vol. 236  (2) , 535-541
Abstract
Acetylcholine has been reported to produce vasodilation or vasoconstriction in the pulmonary circulation of different species. In rabbit lungs, acetylcholine is a potent vasoconstrictor. The present study was undertaken to examine the contractile effects of acetylcholine in arteries isolated from various regions of the rabbit pulmonary vascular bed and in thoracic aorta. Arteries isolated from within the lung were more responsive than extrapulmonary arteries (main pulmonary artery and aorta) to the contractile effects of acetylcholine. In vessels precontracted with norepinephrine, acetylcholine caused biphasic (relaxation-contraction) concentration-response curves. Atropine inhibited acetylcholine-induced contractions in all vessels, whereas pretreatment with cyclooxygenase or thromboxane synthetase inhibitors abolished contractile responses to acetylcholine only in intrapulmonary arteries. In accordance with these findings, acetylcholine caused a 3-fold increase in thromboxane A2 release from intrapulmonary arteries but not from extrapulmonary arteries. Inhibition of thromboxane synthetase abolished this effect of acetylcholine. Endothelium removal decreased contractile responses in intrapulmonary arteries but it did not decrease contractions in extrapulmonary arteries, suggesting that endothelium may contribute to acetylcholine-induced, thromboxane-mediated contractions in intrapulmomary arteries. Indomethacin did not inhibit contractile responses in endothelium-denuded main pulmonary artery or aorta but it abolished the weak contractile responses in intrapulmonary arteries without endothelium, indicating that arterial smooth muscle also was a source of contractile prostanoid biosynthesis enhanced by acetylcholine. These results demonstrate that acetylcholine contracts rabbit intrapulmonary arteries through generation of thromboxane A2 but that a different mechanism is responsible for mediating weaker acetylcholine-induced contractions in extrapulmonary artery and aorta. Furthermore, these data suggest that acetylcholine-induced vasoconstriction observed in intact rabbit lungs is caused by thromboxane A2-mediated contraction of intrapulmonary resistance arteries and that pulmonary vascular endothelium may contribute to this action of acetylcholine.