The role of 5-hydroxytryptamine in the control of pulmonary vascular tone in a rabbit model of pulmonary hypertension secondary to left ventricular dysfunction

The role of 5-hydroxytryptamine (5-HT) in a rabbit model of pulmonary hypertension (PHT) secondary to left ventricular dysfunction was investigated. Following pulmonary artery catheterisation under anaesthesia. 5-HT (1-400 ug kg(-1) i.v.) was administered before and after either 5-HT2A receptor antagonism with ketanserin (0.5 mg kg(-1)) or infusion of the nitric oxide synthase inhibitor, t-NAME (30 mumol min(-1)). Eight week coronary artery ligated rabbits demonstrate increased mean pulmonary arterial pressure (PAP) compared to controls (17.0 +/- 0.5 versus 12.0 +/- 0.5 mmHg, P < 0.001) accompanied by right ventricular hypertrophy. 5-HT alone produced a greater pulmonary pressor response in rabbits with PHT (increase of 7.5 +/- 1.2. n = 12 c.f. 3.5 +/- 0.4 mmHg in shams, it = 12, P < 0.01). Ketanserin had no effect on basal PAP in either PHT or control rabbits but inhibited the response to 5-HT in both groups. The response to 5-HT following L-NAME was increased in both groups and was greater in rabbits with PHT (an increase of 20-1 +/- 2.9, n = 6 c.f. 11.4 +/- 1.8 mmHg, n= 6 P < 0.05). These results suggest that the difference shown in the in vivo pulmonary response to exogenous 5-HT is mediated largely through 5-HT2A, receptors in this model. However, activity of endogenous 5-HT at the 5-HT2A receptors is not responsible for maintaining the raised basal PAP through vasoconstriction in PHT rabbits once PHT has developed. (C) 2004 Elsevier Ltd. All rights reserved.