Effect of clonidine on autonomic nervous system function in two-kidney, one-clip hypertensive rats

Two kidney one clip (2K1C) hypertension in rats is associated with sympathetic hyperactivity. Clonidine, an alpha-2 adrenoceptor agonist, reduces sympathetic activity. The aim of the present study was to investigate the effects of clonidine on mean arterial blood pressure (MAP), heart rate (HR), cardiac sympathetic tonus (ST), and parasympathetic tonus (PT) in conscious 2K1C hypertensive rats. For this purpose, a one week after renal artery clipping or sham operation, we treated the rats with either clonidine (200 ?g/kg/d, orally) or distilled water for two weeks. Then, the rats were instrumented with catheters in the femoral artery and vein to measure MAP and to infuse the drugs, respectively. After a one day of recovery, cardiac ST and PT were determined by HR response to atenolol (1 mg/kg) and atropine methyl nitrate (1 mg/kg), respectively. Spontaneous baroreflex sensitivity was calculated pre-and post-beta 1 blockade, by sequence method. Then, vascular autonomic activity was examined by calculating the decrease in MAP after blockade by hexamethonium bromide (HX). Clonidine increased MAP in both sham-operated (p<0.05) and hypertensive rats (p<0.001). Blockade of beta 1 receptors decreased HR in only distilled water treated sham-operated rats (p<0.01). Clonidine did not affect cardiac ST, and PT in both sham-operated and hypertensive rats. Intrinsic HR was less in clonidine-treated sham-operated rats than distilled water-treated sham-operated rats (p<0.01). MAP decreased in clipped rats more than in sham operated controls after autonomic blockade by hexamethonium under clonidine (p<0.01) or distilled (p<0.05) water treatment. Clonidine did not change significantly the decrease in MAP after the blockade. Clonidine decreased the body weight gain in both clipped (p<0.01) and their sham-operated controls (p<0.001). We conclude that clonidine increased MAP in both 2K1C hypertensive and their sham operated controls without changing cardiac and vascular autonomic activity and baroreflex sensitivity, probably by means of peripheral alpha 2 receptors.