RESUMO
This study evaluated the possible involvement of 5-HT(2B) receptors in long-lasting hypotension to 5-hydroxytryptamine (5-HT), which is predominantly mediated by 5-HT7 receptors, in anaesthetised vagosympathectomized rats. Intravenous injections of 5-HT and 5-carboxamidotryptamine (5-CT) elicited a dose-dependent hypotension that was dose-dependently antagonised by (R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl) ethyl] pyrrolidine (SB-269970; a selective 5-HT7 receptor antagonist), but not by saline. Interestingly, alpha-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine (BW723C86; a 5-HT(2B) receptor agonist) produced vasopressor responses without affecting hypotension to 5-HT. These results suggest that hypotension to 5-HT and 5-CT is mainly mediated by 5-HT7 receptors, whilst the role of 5-HT(2B) receptors seems unlikely.
Assuntos
Hipotensão/metabolismo , Hipotensão/fisiopatologia , Receptor 5-HT2B de Serotonina , Receptores de Serotonina/fisiologia , Serotonina/análogos & derivados , Vagotomia , Animais , Relação Dose-Resposta a Droga , Hipotensão/induzido quimicamente , Masculino , Ratos , Ratos Wistar , Receptor 5-HT2B de Serotonina/fisiologia , Serotonina/farmacologia , Serotonina/toxicidade , Agonistas do Receptor 5-HT2 de Serotonina , Antagonistas do Receptor 5-HT2 de Serotonina , Antagonistas da Serotonina/farmacologiaRESUMO
The present study set out to investigate the pharmacological profile of the cardiovascular responses induced by the antimigraine agent, isometheptene, in pithed rats. For this purpose, intravenous (i.v.) administration of blocking doses of the antagonists prazosin (alpha1; 100 microg/kg), rauwolscine (alpha2; 300 microg/kg), the combination of prazosin (100 microg/kg) plus rauwolscine (300 microg/kg), propranolol (beta; 1000 microg/kg), ritanserin (5-HT2; 100 microg/kg) or equivalent volumes of saline (1 ml/kg) were used. Isometheptene (0.03, 0.1, 0.3, 1 and 3 mg/kg, i.v.) produced dose-dependent increases in heart rate and diastolic blood pressure which were highly reproducible as they remained unaltered after saline. These tachycardic responses to isometheptene remained unaffected after prazosin, rauwolscine, ritanserin or the combination prazosin plus rauwolscine, but were abolished after propranolol. In contrast, the isometheptene-induced vasopressor responses were not significantly modified after the above doses of rauwolscine, ritanserin or propranolol, but were markedly blocked after prazosin or the combination of prazosin plus rauwolscine; the latter blockade did not significantly differ from that produced by prazosin alone. Interestingly, in rats pretreated intraperitoneally (i.p.) with reserpine (5 mg/kg; -24 h), isometheptene-induced tachycardic responses were abolished whereas the corresponding vasopressor responses were markedly attenuated and subsequently blocked by prazosin. It is concluded that isometheptene-induced tachycardic responses seem to involve only an indirect (tyramine-like action) mechanism mediated by beta-adrenoceptors, whilst the corresponding vasopressor responses are mediated by a predominantly indirect (tyramine-like action), as well as a minor direct (alpha1-adrenoceptors), sympathomimetic mechanism.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Metilaminas/farmacologia , Transtornos de Enxaqueca/tratamento farmacológico , Taquicardia/induzido quimicamente , Antagonistas Adrenérgicos alfa/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Estado de Descerebração , Relação Dose-Resposta a Droga , Frequência Cardíaca/efeitos dos fármacos , Injeções Intravenosas , Masculino , Metilaminas/administração & dosagem , Metilaminas/toxicidade , Ratos , Ratos Wistar , Reserpina/farmacologia , Antagonistas da Serotonina/farmacologiaRESUMO
Dihydroergotamine produces external carotid vasoconstriction in vagosympathectomized dogs by 5-HT(1B/1D) receptors and alpha(2)-adrenoceptors. This study identified the specific subtypes involved in this response. One-minute intracarotid infusions of dihydroergotamine (5.6-10 microg/min) dose-dependently decreased external carotid blood flow without affecting blood pressure or heart rate. This response was: (1) partly blocked in dogs pretreated intravenously with the antagonists SB224289 (5-HT(1B); 2,3,6,7-tetrahydro-1'-methyl-5-[2'-methyl-4' (5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carbonyl]furo[2,3-f]indole-3-spiro-4'-piperidine hydrochloride), rauwolscine (alpha(2)), BRL44408 (alpha(2A); 2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5-dihydroimidazole) or MK912 (alpha(2C); (2S,12bS)-1'3'-dimethylspiro(1,3,4,5',6,6',7,12b-octahydro-2Hbenzo[b]furo[2,3-a]quinazoline)-2,4'-pyrimidin-2'-one); (2) markedly blocked after SB224289 plus rauwolscine; and (3) unaffected after BRL15572 (5-HT(1D); 1-(3-chlorophenyl)-4-[3,3-diphenyl (2-(S,R) hydroxypropanyl) piperazine] hydrochloride) or imiloxan (alpha(2B)). Therefore, the above response involves 5-HT(1B) receptors and alpha(2A/2C)-adrenoceptors.