IMPAIRED BASAL SYMPATHETIC TONE AND ALPHA(1)-ADRENERGIC RESPONSIVENESS IN ASSOCIATION WITH THE HYPOTENSIVE EFFECT OF MELATONIN IN SPONTANEOUSLY HYPERTENSIVE RATS

Early investigations have suggested a relationship between hypertensio n and melatonin, a pineal hormone. The aims of this study were to eval uate the implication of the sympathetic nervous system in the acute ef fect of melatonin on blood pressure in conscious 12-week-old spontaneo usly hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), and to deter mine whether the hypotensive effect of melatonin is associated with al terations in pre-or postsynaptic mechanisms. Melatonin, 10 mg/kg, prod uced a sustained time-dependent decrease of mean arterial pressure onl y in SHR without changes in heart rate in both groups. Until 20 min af ter melatonin administration, plasma epinephrine (EPI) levels were red uced by about 60% in both groups, but norepinephrine (NE) levels were decreased only in SHR by about 30%. The nitroprusside-induced hypotens ion responses and the associated increases in heart rate were similar in both groups before or after administration of melatonin. Unexpected ly, the sympathetic reactivity to nitroprusside, evaluated by the incr eases in NE and EPI, was markedly enhanced after melatonin treatment i n both WKY and SHR. The stimulation induced [H-3]norepinephrine releas e from isolated atria was not altered by melatonin in SHR. In cultured aortic vascular smooth muscle cells, the basal and phenylephrine indu ced inositol phosphate formations were greater in SHR, and the melaton in pretreatment dose dependently attenuated the phenylephrine response s in cells from both WKY and SHR. Therefore the hypotensive action of melatonin appears to be associated with an inhibition of basal sympath oadrenal tone and could also be mediated partly by the blockade of pos tsynaptic alpha(1)-adrenergic receptor-induced inositol phosphate form ation. (C) 1998 American Journal of Hypertension, Ltd.