zimeldine and Hypertension

A naloxone-reversible long-lasting depressor response induced by a prolonged low frequency stimulation of the sciatic nerve in conscious spontaneously hypertensive rats (SHRs) was reported in a previous paper. In the present study pharmacological tools were used to further investigate the neurotransmitters involved in this phenomenon. Naloxone infusion (20--25 mg/kg/h following a bolus dose of 10 mg/kg i.v.) attenuated significantly the depressor response, while dexamethasone pretreatment had no such effect, suggesting an important role of the brain endorphin system, but not of the pituitary beta-endorphin, in this depressor response. Since the concomitant increase in pain threshold produced by the sciatic stimulation exhibited a different time course of development and naloxone reversibility, it is suggested that the depressor response and the hypalgesic effect produced by the same stimulation are mediated via different types of opiate receptors in the brain. On the other hand, PCPA abolished the post-stimulatory depressor response whereas 5-HTP and zimelidine had additive effects on the sciatic stimulation-induced depressor response, suggesting the involvement of central serotonin systems in the mechanism of the response. The interaction between the central endorphin and the serotonin systems in the mediation of the post-stimulatory depressor response is discussed.

Topics: 5-Hydroxytryptophan; Animals; Blood Pressure; Brompheniramine; Dexamethasone; Electric Stimulation; Endorphins; Heart; Heart Rate; Hypertension; Naloxone; Neural Inhibition; Nociceptors; Rats; Rats, Inbred Strains; Sciatic Nerve; Serotonin; Synaptic Transmission; Zimeldine