Hypotensive effect of clonidine during sodium depletion in the rat.

Abstract

Clonidine was nonhypotensive in conscious unrestrained rats mantained on a normal Na intake. Clonidine caused a dose-related hypotension in conscious unrestrained rats subjected to Na depletion via furosemide. The plasma renin activity of normal and Na-depleted rats was reduced after the administration of clonidine (100 .mu.g/kg, i.v.) by 22.8% and 34.4%, respectively. I.v. infusion of an angiotensin II antagonist, 1-Sar-8-Ala-angiotensin II, caused a significant reduction of arterial blood pressure in Na-depleted rats but not in normal rats. Similarly, bilateral nephrectomy reduced arterial blood pressure and completely abolished the hypotensive effect of clonidine in Na-depleted rats. S.c. administration of chlorisondamine caused a significantly greater reduction of arterial blood pressure in Na-depleted rats than it did in normal rats. Treatment of normal and Na-depleted rats with 6-hydroxydopamine reduced the arterial blood pressure of both groups to approximately 85 mm Hg and completely abolished the hypotensive effect of clonidine in the Na-depleted rats. Clonidine acts at some site in the sympathetic nervous system of Na-depleted rats to inhibit renal nerve activity with a resultant suppression of renin secretion and a reduction of the angiotensin II-maintained arterial blood pressure. A similar sequence of events occurring in normal rats would not result in hypotension because their arterial blood pressure is not maintained by angiotensin II.