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 moxonidine increases sodium excretion without alteration of blood pressure. In the present study we determined whether this natriuretic action was mediated through a decrease in activity of the sympathetic nervous system, as has been reported for the antihypertensive action of this compound. Interruption of the sympathetic nervous system was achieved with prazosin (α‐adrenoceptor antagonist) and renal denervation. 2 . In pentobarbitone‐anaesthetized Sprague‐Dawley rats, intracerebroventricular (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 controls. In the presence of prazosin, i.c.v. injection of moxonidine failed 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 clearance. The increase in sodium excretion and osmolar clearance were completely attenuated in renal denervated rats, however, urine flow rate was still increased and this was secondary to the increase in free water clearance which remained intact. 4 . These results indicate the importance of an intact sympathetic nervous system in the renal response to i.c.v. moxonidine. Moreover, the differential antagonism of these interventions on solute and water excretion indicate that they may be mediated at two separate sites and/or receptors following i.c.v. moxonidine.