Hypotensive effect of clonidine during sodium depletion in the rat

Abstract

Clonidine was nonhypotensive in conscious unrestrained rats maintained on a normal sodium intake. In contradistinction, clonidine caused a dose related hypotension in conscious unrestrained rats subjected to sodium depletion via furosemide. The plasma renin activity of normal and sodium depleted rats was reduced after the administration of clonidine (100 μg/kg,iv) by 22.8% and 34.4%, respectively. Intravenous infusion of an angiotensin II antagonist, 1 Sar 8 Ala angiotensin II, caused a significant reduction of arterial blood pressure in sodium depleted rats but not in normal rats. Similarly, bilateral nephrectomy reduced arterial blood pressure and completely abolished the hypotensive effect of clonidine in sodium depleted rats. Subcutaneous administration of chlorisondamine caused a significantly greater reduction of arterial blood pressure in sodiumdepleted rats than it did in normal rats. Treatment of normal and sodium 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 sodium depleted rats. The data presented in this paper are consistent with the conclusion that clonidine acts at some site in the sympathetic nervous system of sodium 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.