RENAL DENERVATION ALTERED THE HEMODYNAMIC AND RENAL EFFECTS FOLLOWINGINTRACEREBROVENTRICULAR ADMINISTRATION OF THE I-1-IMIDAZOLINE RECEPTOR AGONIST, RILMENIDINE, IN PENTOBARBITAL-ANESTHETIZED RATS

Previous studies have reported on the effects of intracerebroventricul ar (icv) administration of the I-1-imidazoline receptor agonist moxoni dine. In the present study, the relationship between increasing doses of the I-1-agonist rilmenidine (administered icv) with blood pressure and renal function has been determined. Moreover, the importance of th e renal nerves in this response have also been assessed. In pentobarbi tone anesthetized rats, icv rilmenidine (30, 100, 300 nmol in 5 mu l) produced a dose related decrease in blood pressure and heart rate. Uri ne flow was not altered at the lower doses although at the highest dos e (300 nmol) the increase approached significance (p = 0.06). Sodium e xcretion and osmolar clearance were not altered. Free water clearance was increased at 100 and 300 nmol rilmenidine (p < 0.05). Consistent w ith the above dose response studies, in sham denervated rats icv rilme nidine (300 nmol) decreased blood pressure and increased free water cl earance. In rats having undergone renal denervation, baseline levels o f urine flow rate, sodium excretion and osmolar clearance were increas ed. In these denervated rats, icv rilmenidine (300 nmol) failed to dec rease blood pressure. Urine flow rate was increased with a decrease in sodium excretion and osmolar clearance. Free water clearance was incr eased. These results indicate the importance of the renal nerves in me diating the acute decrease in blood pressure following icv administrat ion of the I-1-imidazoline receptor agonist rilmenidine. The increase in free water clearance seen following icv rilmenidine appears to be m ediated independent of the renal nerves. The changes associated with s odium excretion on the contrary are dependent on intact renal nerves. Copyright (C) 1996 Elsevier Science Ltd.