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.
Shaw
A M
AM
School of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, G4 0BA, UK. A.M.Sha@gcal.ac.uk
Brown
C
C
Irvine
J
J
Bunton
D C
DC
MacDonald
A
A
D000818:Animals; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D011651:Pulmonary Artery / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*
D018340:Receptors, Adrenergic, alpha-1; D011985:Receptors, Serotonin; D009569:Nitric Oxide; D012701:Serotonin