Role of the 5-HT(2A)receptor and alpha(1)-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(2A)receptors and alpha(1)-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. The alpha(1)-adrenoceptor antagonists prazosin, HV723 and phentolamine produced concentration-dependent rightward shifts of the 5-HT concentration-response curves (CRC) consistent with an action at alpha(1)-adrenoceptors. The 5-HT(2)receptor antagonists ritanserin, ketanserin and methysergide produced rightward shifts that were less than would have been predicted for an action solely at 5-HT(2A)receptors. 5-HT and phenylephrine CRCs were shifted to the left by l -NAME. Endothelium denudation also increased the tissue sensitivity to 5-HT. In the presence of l -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 the alpha(1)-adrenoceptor class and the 5-HT(2A)receptor 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 by alpha(1)-adrenoceptors; (c) inhibition of endogenous nitric oxide potentiates the 5-HT(2A)receptor-mediated component of the contraction. Copyright 2000 Academic Press.

Citation

A M Shaw, C Brown, J Irvine, D C Bunton, A MacDonald. Role of the 5-HT(2A)receptor and alpha(1)-adrenoceptor in the contractile response of rat pulmonary artery to 5-HT in the presence and absence of nitric oxide. Pulmonary pharmacology & therapeutics. 2000;13(6):277-85

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PMID: 11061982

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