Natriuretic effect of rilmenidine in anesthetized rats

Rilmenidine binds to alpha 2-adrenoceptors and imidazoline receptors in the central nervous system and the kidney. To test the hypothesis that rilmenidine would increase sodium excretion, renal function was studied in rats with innervated and denervated kidneys to distinguish between indirect (via renal sympathetic nerves) and direct effects of rilmenidine on the kidney. Standard clearance techniques were used in Wistar rats anesthetized with thiobutabarbital to measure renal function during 80 minutes of infusion of 0.9% NaCl or rilmenidine (20 or 50 micrograms.kg-1.min-1 intravenously). Snares on abdominal arteries were used to offset hypotension induced by rilmenidine. Heart rate decreased by 80-120 beats/min with either dose of rilmenidine. At 20 micrograms.kg-1.min-1, rilmenidine increased total and fractional excretion of sodium and clearance of osmoles while decreasing free water clearance from innervated kidneys. There were no changes in these variables in chronically denervated kidneys. Direct recording of renal sympathetic nerve activity showed a progressive, marked decrease in nerve activity during the low-dose infusion of rilmenidine. At 50 micrograms.kg-1.min-1, rilmenidine produced a differential effect on the clearance of osmoles by innervated and denervated kidneys but both kidneys had an increase in free water clearance. The data indicate that rilmenidine increases sodium excretion indirectly in anesthetized rats by decreasing renal sympathetic nerve activity. At doses and infusion periods used in these studies, there was no evidence for a direct effect of rilmenidine on sodium excretion. The increase in free water clearance seen with the high dose of rilmenidine suggests that the inhibitory effect of alpha 2-adrenoceptor activation on vasopressin is involved at this dose.(ABSTRACT TRUNCATED AT 250 WORDS)