Changes in systemic and regional haemodynamics during 5-HT7 receptor-mediated depressor responses in rats

The 5-hydroxytryptamine (5-HT)-induced late depressor response in rats is mainly mediated by vascular 5-HT7 receptors. The present study was devoted to determining the systemic and regional haemodynamic changes during this response, with particular emphasis on localising vascular beds that may contribute to the increase in total systemic vascular conductance. In vagosympathectomised, pentobarbital-anaesthetised rats pretreated with the 5-HT2 receptor antagonist ritanserin (50 mu g kg(-1), i.v.), 5-HT (1, 3 and 10 mu g kg(-1) min(-1) during 10 min; i.v.) produced a dose-dependent decrease in mean arterial blood pressure by up to 46+/-3%. This decrease was accompanied by increases in systemic vascular conductance by up to 83+/-15%; cardiac output was unaffected. 5-HT increased regional vascular conductance in skeletal muscle, carcass, mesentery/pancreas and adrenals by up to 740+/-141%, 117+/-18%, 135+/-26% and 88+/-22%, respectively, but decreased 'lung' (mainly arteriovenous anastomotic) conductance by up to 81+/-2%. Pretreatment with R(+)lisuride (100 mu g kg(-1), i.v.) abolished all 5-HT-induced systemic and regional haemodynamic effects. In contrast, i.v. pretreatment with S(-)lisuride (100 mu g kg(-1)) or GR127935 (300 mu g kg(-1)) did not affect the 5-HT-induced systemic haemodynamic changes. The above results suggest that hypotension induced via 5-HT7 receptor activation was exclusively caused by vasodilatation of the systemic vasculature, confined to skeletal muscle, carcass, mesentery/pancreaa and adrenal vascular beds. Furthermore, this study shows that blockade of vasorelaxant 5-HT7 receptors by lisuride is stereoselective.