Role of the 5-HT2AReceptor and α1-adrenoceptor in the Contractile Response of Rat Pulmonary Artery to 5-HT in the Presence and Absence of Nitric Oxide

This study investigated the role of 5-HT_2Areceptors andα₁ -adrenoceptors in the contractile response to 5-HT in the first branch pulmonary artery of the rat and their interaction with endogenous nitric oxide. 5-HT and phenylephrine induced concentration-dependent contractions. Theα₁ -adrenoceptor antagonists prazosin, HV723 and phentolamine produced concentration-dependent rightward shifts of the 5-HT concentration-response curves (CRC) consistent with an action at α₁-adrenoceptors. The 5-HT₂receptor antagonists ritanserin, ketanserin and methysergide produced rightward shifts that were less than would have been predicted for an action solely at 5-HT_2Areceptors. 5-HT and phenylephrine CRCs were shifted to the left by -NAME. Endothelium denudation also increased the tissue sensitivity to 5-HT. In the presence of -NAME, ketanserin produced greater antagonism of the 5-HT CRC but not the phenylephrine CRC. Ketanserin also produced greater antagonism of the 5-HT CRC in endothelium denuded rings compared with endothelium intact rings. These findings indicate (a) that both theα₁ -adrenoceptor class and the 5-HT_2Areceptor is involved in the contractile response to 5-HT; (b) in the presence of endogenous nitric oxide the contractile response to 5-HT is mediated predominently byα₁ -adrenoceptors; (c) inhibition of endogenous nitric oxide potentiates the 5-HT_2Areceptor-mediated component of the contraction.