Beneficial effects of renal denervation and prazosin on GFR and renal blood flow after cyclosporine in rats

Abstract

We have previously shown that both acute infusion of cyclosporine and chronic intraperitoneal cyclosporine result in decreased renal blood flow in rats. This effect of cyclosporine infusion was mediated via the sympathetic nervous system. In this study, renal denervation was found to also prevent the decrease in glomerular filtration rate after cyclosporine infusion. Male Sprague-Dawley rats underwent unilateral renal denervation and three days later inulin clearance was measured following infusion of cyclosporine (20 mg/kg). GFR fell by 43% in innervated kidneys, but remained normal in denervated kidneys. In addition, administration of the alpha-adrenergic antagonist prazosin prevented the rise in serum creatinine and the fall in renal blood flow associated with chronic cyclosporine administration (20 mg/kg intraperitoneally for 7 days). These findings further support the hypothesis that sympathetic nervous system-mediated vasoconstriction is responsible for renal dysfunction in rats after acute and chronic cyclosporine administration.