MECHANISM OF SUPPRESSION OF VASOPRESSIN AND ADRENOCORTICOTROPIC HORMONE-SECRETION BY CLONIDINE IN ANESTHETIZED DOGS

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 229  (1) , 1-8
Abstract
The mechanism of the suppression of vasopressin and ACTH secretion by clonidine was studied in dogs. Injection of clonidine (30 .mu.g/kg i.v.) produced an initial increase in arterial pressure followed by hypotension, decreased heart rate, increased right atrial pressure and decreased plasma renin activity. Plasma vasopressin concentration decreased from 14.6 .+-. 3.0 to 2.2 .+-. 0.4 pg/ml (P < 0.01), and this was accompanied by increase in urine volume and free water clearance from 0.15 .+-. 0.02 to 1.03 .+-. 0.28 and -0.50 .+-. 0.05 to 0.30 .+-. 0.27 ml/min, respectively (P < 0.01), and a decrease in urinary osmolality from 1450 .+-. 124 to 372 .+-. 97 mOsmol/kg of H2O (P < 0.01). Plasma corticosteroid concentration, used an index of ACTH secretion, decreased from 8.9 .+-. 1.6 to 2.2 .+-. 0.3 .mu.g/dl (P < 0.01). Plasma osmolality did not change. Pretreatment of dogs with the .alpha. adrenoceptor antagonist yohimbine (2 mg/kg i.p.) blocked all cardiovascular, endocrine and renal responses to clonidine. Bilateral cervical vagotomy did not block the suppression of vasopressin or corticosteroid secretion by clonidine. Intraventricular injection of yohimbine blocked the hypotension and suppression of plasma corticosteroid concentration produced by clonidine but did not block the decrease in plasma vasopressin concentration or the associated renal effects of clonidine. Intracarotid infusion of clonidine caused small decreases in plasma vasopressin and corticosteroid concentrations even though blood pressure decreased by 22 mm Hg. Intraventricular and intravertebral clonidine had no significant effect on plasma vasopressin or corticosteroid concentrations. Oxymetazoline (i.v.), a clonidine-like imidazoline that does not cross the blood-brain barrier, suppressed plasma vasopressin and corticosteroid concentrations although not as effectively as i.v. clonidine. Clonidine can evidently suppress vasopressin and ACTH secretion by a number of different mechanisms. These include elevation of arterial pressure, increased central venous pressure and a direct action in the CNS. When any one of these mechanisms is eliminated, clonidine can still suppress the secretion of these hormones via one or both of the remaining mechanisms. A feature which is common to all mechanisms appears to be stimulation of .alpha. adrenoceptors, because the suppression of vasopressin and ACTH secretion can be blocked by yohimbine.