Role of dopamine in the inhibition of vasopressin secretion by L-dopa in carbidopa-treated dogs.

Abstract

SUMMARY Elevation of brain catecholamine levels by systemic administration of L-dopa in dogs pretreated with the dopa decarboxylase inhibitor carbidopa inhibits the secretion of vasopressin and adrenocorticotropic hormone (ACTH) and decreases arterial blood pressure. The aim of the present study was to determine 1) whether the inhibition of vasopressin secretion is mediated by dopamine or norepinephrine, both of which have been implicated in the control of vasopressin secretion, and 2) whether the decrease in vasopressin secretion contributes to the suppression of ACTH secretion and fall in blood pressure produced by L-dopa. This was accomplished by comparing the effects of dopamine and a-adrenergic receptor antagonists on vasopressin, ACTH, and blood pressure responses to L-dopa. The effect of a specific antagonist of the vasoconstrictor action of vasopressin also was studied. Injection of L-dopa (20 mg/kg i.v.) in dogs pretreated with carbidopa (20 mg/kg i.v.) caused reductions in plasma vasopressin concentration (from 16.0 ± 4.8 to 3.8 ± 0.9 pg/ml; p<0.05), plasma ACTH concentration (from 96.0 ± 20.4 to 49.2 ± 10.0 pg/ml; p<0.05), and mean arterial pressure (from 121 ± 6 to 78 ± 5 mm Hg; p<0.05). Pretreatment with pimozide (1 mg/kg i.p.) completely blocked the inhibition of vasopressin secretion by L-dopa but failed to block the suppression of ACTH secretion (57.6 ± 11.8 to 34.0 ± 5.1 pg/ml; p<0.05) or the decrease in mean arterial pressure (126 ± 5 to 93 ± 7 mm Hg; p<0.05). The antihypertensive effect of L-dopa was reduced by prazosin (97 ± 3 to 82 ± 6 mm Hg; p<0.05) and blocked by yohimbine, but neither drug blocked the suppression of plasma vasopressin or ACTH. Administration of a vasopressin antagonist did not decrease arterial pressure and caused only a small, delayed reduction in plasma ACTH concentration. These studies provide evidence that the inhibition of vasopressin secretion by L-dopa is mediated by dopamine rather than by norepinephrine. The failure of a vasopressin antagonist to significantly decrease blood pressure or ACTH secretion and the dissociation of the effects of L-dopa on vasopressin release, blood pressure, and ACTH secretion argue against a major role for vasopressin in the blood pressure and ACTH responses to L-dopa. Received December 13, 1985; accepted April 15, 1986. variety of stimuli. 3 4 In addition, the release of vasopressin can be altered by central administration of catecholamines, other adrenergic agonists, and adrenergic blocking drugs.5 " 9 Although there is general agreement that central catecholamines are involved in the control of vasopressin release, there is still controversy concerning the nature of this control. Many investigators have concluded that brain catecholamines act to inhibit vasopressin release, 6 ' '• 10~15 while others have presented evidence for a stimulatory effect. 8 ' l6~18 In addition, the relative importance of dopamine and norepinephrine is not clear.In a previous investigation in this laboratory, we reported that intravenous administratio...