The importance of the renal sympathetic nerves in the natriuretic response to imidazoline receptor agonists

Abstract

In our preliminary dose--response study two I1 -imidazoline receptor agonists (rilmenidine and moxonidine) and two _ 2-adrenoceptor agonists (clonidine and guanfacine) were investigated. Based on those studies, we selected rilmenidine (10 nmol/kg/min) and guanfacine (10 nmol/kg/min) for our further studies. The renal sympathetic nerves have been proposed to be important in the renal actions of imidazoline receptor and _2-adrenoceptor agonists. We therefore determined the effects of acute renal denervation on the diuretic and natriuretic actions of rilmenidine, guanfacine and furosemide. The dose of furosemide (0.1 mg/kg) was selected based on the previous experiments in our laboratory. Male Sprague-Dawley rats underwent unilateral nephrectomy 7 to 10 days prior to the experimental day. Animals were anesthetized with pentobarbital. A tracheotomy was performed and the animal allowed breathing spontaneously. The carotid artery was cannulated for blood pressure and heart rate monitoring and the left jugular vein was cannulated for infusion of study drugs. The left kidney was exposed by a flank incision and the ureter was cannulated for the collection of urine. The kidney was denervated surgically and by painting the renal artery with phenol (10%) in 95% ethyl alcohol. (Abstract shortened by UMI.)