Influence of 5-hydroxytryptamine on the pressor responses induced by norepinephrine and electrical sympathetic stimulation in the pithed rat.
Serotonin (5-hydroxytryptamine; 5-HT) modifies the responses to several vasoconstrictor stimuli prejunctionally and/or postjunctionally. The present study analyzed the effects of 5-HT on the pressor responses induced by norepinephrine (NE) or electrical sympathetic stimulation in pithed rats. Responses to intravenous (i.v.) NE (0.03-3 micrograms/kg) or electrical stimulation at increasing frequencies (0.1-3 Hz) were evaluated before and during continuous i.v. infusions of physiological saline (0.01 ml/min) or 5-HT (1-10 micrograms/kg x min). The effects of 5-HT on the tachycardic responses to NE and sympathetic stimulation were studied in parallel. The increases in diastolic blood pressure and heart rate produced by NE were not modified by 5-HT. In contrast, 5-HT significantly and dose-dependently inhibited the increases in diastolic blood pressure - but not those in heart rate - produced by stimulation of the appropriate spinal segments. These effects of 5-HT were more pronounced on the responses to lower frequencies of stimulation. It is suggested that 5-HT inhibits the electrically induced pressor responses by a prejunctional mechanism which would lead to a reduction of neurotransmitter release from the sympathetic nerves supplying the systemic vasculature. The selective stimulation of this inhibitory mechanism might represent a new approach for the development of novel antihypertensive agents.
Terrón
J A
JA
Departamento de Farmacología y Toxicología, CINVESTAV, I.P.N., México, D.F.
Sánchez-López
A
A
Ramírez-San Juan
E
E
Castillo
C
C
Villalón
C M
CM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003655:Decerebrate State / Q000503:physiopathology*; D003864:Depression, Chemical; D003971:Diastole / Q000187:drug effects; D004347:Drug Interactions; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects*; D007262:Infusions, Intravenous; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000819:agonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D013610:Tachycardia / Q000209:etiology / Q000517:prevention & control; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D012701:Serotonin; D009638:Norepinephrine