Impaired basal sympathetic tone and alpha1-adrenergic responsiveness in association with the hypotensive effect of melatonin in spontaneously hypertensive rats.
Early investigations have suggested a relationship between hypertension and melatonin, a pineal hormone. The aims of this study were to evaluate the implication of the sympathetic nervous system in the acute effect of melatonin on blood pressure in conscious 12-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), and to determine whether the hypotensive effect of melatonin is associated with alterations in pre- or postsynaptic mechanisms. Melatonin, 10 mg/kg, produced a sustained time-dependent decrease of mean arterial pressure only in SHR without changes in heart rate in both groups. Until 20 min after melatonin administration, plasma epinephrine (EPI) levels were reduced by about 60% in both groups, but norepinephrine (NE) levels were decreased only in SHR by about 30%. The nitroprusside-induced hypotension responses and the associated increases in heart rate were similar in both groups before or after administration of melatonin. Unexpectedly, the sympathetic reactivity to nitroprusside, evaluated by the increases in NE and EPI, was markedly enhanced after melatonin treatment in both WKY and SHR. The stimulation induced [3H]-norepinephrine release from isolated atria was not altered by melatonin in SHR. In cultured aortic vascular smooth muscle cells, the basal and phenylephrine induced inositol phosphate formations were greater in SHR, and the melatonin pretreatment dose dependently attenuated the phenylephrine responses in cells from both WKY and SHR. Therefore the hypotensive action of melatonin appears to be associated with an inhibition of basal sympathoadrenal tone and could also be mediated partly by the blockade of postsynaptic alpha1-adrenergic receptor-induced inositol phosphate formation.
K-Laflamme
A
A
Department of Pharmacology, Faculty of Medicine, Université de Montréal, Québec, Canada. laflaman@ere.umontreal.ca
Wu
L
L
Foucart
S
S
de Champlain
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000502:physiology; D012018:Reflex / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
D002395:Catecholamines; D010716:Phosphatidylinositols; D018340:Receptors, Adrenergic, alpha-1; D008550:Melatonin; D009638:Norepinephrine