CENTRAL AND RENAL I-1 IMIDAZOLINE PREFERRING RECEPTORS - 2 UNIQUE SITES MEDIATING NATRIURESIS IN THE RAT

Based on previous studies we postulated that, whereas the natriuresis observed following intracerebroventricular (i.c.v.) moxonidine was med iated by a decrease in renal sympathetic nerve activity, the natriures is observed following intrarenal (i.r.) infusion of moxonidine was med iated by a direct stimulation of renal I-1-imidazoline preferring rece ptors. Sprague-Dawley rats were unilaterally nephrectomized and i.c.v. cannulated 7 to 10 days and 3 days prior to the day of the experiment , respectively. On the day of the experiment, rats were anesthetized ( pentobarbital) and the renal function was isolated. Administration of i.c.v. as well as i.r. moxonidine produced an increase in sodium excre tion and urine flow fate. Pretreatment with intravenous prazosin (0.15 mg/kg) completely attenuated the response to i.c.v. moxonidine (1 nmo l/5 mu l) but only slightly altered the response to i.r. moxonidine (3 nmol/kg/min). Conversely, intravenous pretreatment with the imidazoli ne preferring receptor antagonist idazoxan (0.3 mg/kg) completely bloc ked the response to i.r. moxonidine (3 nmol/kg/min) without altering t he response to i.c.v. moxonidine (0.3 nmol/kg). These results would be consistent with the natriuresis observed following i.c.v. moxonidine as being mediated by imidazoline preferring receptors located centrall y, whereas that following i.r. moxonidine was mediated directly by ren al imidazoline preferring receptors, with a small component of this re sponse conceivably due to activation of central imidazoline preferring receptors. In summary, the antihypertensive effect of imidazoline pre ferring receptor agonists may be associated with a natriuresis that is due to stimulation of these receptors, found both peripherally (renal ) and centrally.