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 severa l vasoconstrictor stimuli prejunctionally and/or postjunctionally. The present study analyzed the effects of 5-HT on the presser responses i nduced by norepinephrine (NE) or electrical sympathetic stimulation in pithed rats. Responses to intravenous (i.v.) NE (0.03 - 3 mu g/kg) or electrical stimulation at increasing frequencies (0.1 - 3 Hz) were ev aluated before and during continuous i.v. infusions of physiological s aline (0.01 ml/min) or 5-HT (1 - 10 mu g/kg x min). The effects of 5-H T on the tachycardic responses to NE and sympathetic stimulation were studied in parallel. The increases in diastolic blood pressure and hea rt fate produced by NE were not modified by 5-HT. In contrast, 5-HT si gnificantly and dose-dependently inhibited the increases in diastolic blood pressure but not those in heart rate - produced by stimulation o f the appropriate spinal segments. These effects of 5-HT were more pro nounced on the responses to lower frequencies of stimulation. It is su ggested that 5-HT inhibits the electrically induced presser responses by a prejunctional mechanism which would lead to a reduction of neurot ransmitter release from the sympathetic nerves supplying the systemic vasculature. The selective stimulation of this inhibitory mechanism mi ght represent a new approach for the development of novel antihyperten sive agents.