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Naunyn Schmiedebergs Arch Pharmacol ; 359(4): 331-8, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10344532

RESUMO

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 microg kg(-1), i.v.), 5-HT (1, 3 and 10 ug 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+/-14%, 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 microg kg(-1), i.v.) abolished all 5-HT-induced systemic and regional haemodynamic effects. In contrast, i.v. pretreatment with S(-)lisuride (100 microg kg(-1)) or GR127935 (300 microg 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/pancreas and adrenal vascular beds. Furthermore, this study shows that blockade of vasorelaxant 5-HT7 receptors by lisuride is stereoselective.


Assuntos
Pressão Sanguínea/fisiologia , Hemodinâmica/fisiologia , Receptores de Serotonina/fisiologia , Glândulas Suprarrenais/irrigação sanguínea , Animais , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Hemodinâmica/efeitos dos fármacos , Rim/irrigação sanguínea , Lisurida/química , Lisurida/farmacologia , Pulmão/irrigação sanguínea , Masculino , Músculo Esquelético/irrigação sanguínea , Oxidiazóis/farmacologia , Pâncreas/irrigação sanguínea , Piperazinas/farmacologia , Ratos , Ratos Wistar , Valores de Referência , Serotonina/farmacologia , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Estereoisomerismo , Volume Sistólico/efeitos dos fármacos , Capacitância Vascular/efeitos dos fármacos
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