THE ROLE OF THE PERIPHERAL SYMPATHETIC NERVOUS-SYSTEM IN THE NATRIURESIS FOLLOWING CENTRAL ADMINISTRATION OF AN I-1 IMIDAZOLINE AGONIST, MOXONIDINE

1 Central administration of the I-1-imidazoline receptor agonist moxon idine increases sodium excretion without alteration of blood pressure. In the present study we determined whether this natriuretic action wa s mediated through a decrease in activity of the sympathetic nervous s ystem, as has been reported for the antihypertensive action of this co mpound. Interruption of the sympathetic nervous system was achieved wi th prazosin (alpha(1)-adrenoceptor antagonist) and renal denervation. 2 In pentobarbitone-anaesthetized Sprague-Dawley rats, intracerebroven tricular (i.c.v.) injection of moxonidine alone increased urine volume and sodium excretion. Prazosin (0.15 mg kg(-1), i.v.) alone decreased urine flow rate and sodium excretion as compared to the vehicle contr ols. In the presence of prazosin, i.c.v. injection of moxonidine faile d to increase sodium excretion or urine volume as compared to animals which received the prazosin alone. 3 The administration of moxonidine (i.c.v.) to sham renal-denervated animals caused an increase in urine flow rate, urine sodium excretion, osmolar clearance and free water cl earance. The increase in sodium excretion and osmolar clearance were c ompletely attenuated in renal denervated rats, however, urine flow rat e was still increased and this was secondary to the increase in free w ater clearance which remained intact. 4 These results indicate the imp ortance of an intact sympathetic nervous system in the renal response to i.c.v. moxonidine. Moreover, the differential antagonism of these i nterventions on solute and water excretion indicate that they may be m ediated at two separate sites and/or receptors following i.c.v. moxoni dine.