Central 5-hydroxytryptamine (5-HT) receptors in blood pressure regulation.
Both intravenous and central administration of ketanserin, a 5-HT2 receptor antagonist, decrease blood pressure and sympathetic nerve activity, suggesting a central origin of its effects. However, ketanserin also possesses alpha 1-adrenoceptor blocking properties. Selective 5-HT2 receptor antagonists devoid of alpha 1-adrenoceptor blocking properties, e.g. LY 53857 and cinanserin, fail to reduce blood pressure and sympathetic nerve activity. In addition, 5-HT2 receptor agonists increase blood pressure and sympathetic nerve discharge. Therefore, it seems improbable that blockade of central 5-HT2 receptors alone could lead to a reduction in blood pressure. In contrast, the selective 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan decrease blood pressure and heart rate by a centrally-mediated decrease in sympathetic tone and an increase in vagal tone. The sympatho-inhibitory effects of 5-HT1A receptor agonists result from the stimulation of postsynaptic 5-HT1A receptors within the ventrolateral pressor area. These results suggest that selective 5-HT1A receptor agonists acting in the central nervous system could be developed for the treatment of hypertension. Indeed, drugs such as flesinoxan and urapidil are effective in this setting.
Dabiré
H
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INSERM U 337, Faculté de Médecine Broussais Hôtel-Dieu, Paris.
D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007650:Ketanserin / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D007650:Ketanserin; D011224:Prazosin