PS 01-21] RENAL DENERVATION PROTECTS RENAL FUNCTION BY SUPPRESSING NAD(P)H OXIDASE ACTIVITY IN DAHL SALT-SENSITIVE RATS

Abstract

Objective: Sympathetic activity is increased in CKD patients and plays an important and distinct role in renal disease-associated hypertension. Indeed, sympathetic activation is of crucial importance for both the raised blood pressure and the high morbidity and mortality of end-stage renal disease. So we investigated whether renal denervation protects renal function through an anti-oxidative effect. Design and Method: Dahl salt sensitive rats in two groups had the right kidney removed (uninephrectomy; Nx) and those in the other two groups had sham surgery (DL group or DH group). Two weeks later, half of the Nx group underwent left renal denervation (Nx-RDNx group; n = 10) and the other half had sham surgery (Nx-Sham; n = 10). The DL group received a 0.3% salt diet and the DH, Nx-RDNx, and Nx-Sham groups received an 8% salt diet after renal denervation or sham operation. After a further 6 weeks, kidney function and the renal tissue were assessed. Results: Blood pressure, heart rate, body weight, kidney weight and urinary sodium excretion did not differ between Nx-RDNx and Nx-Sham group. Creatinine clearance and urinary albumin excretion were significantly lower in the Nx-RDNx group than in the Nx-Sham group. Desmin staining was lower in Nx-RDNx compared with Nx-Sham. Fluorescent staining for reactive oxygen species in isolated glomeruli was significantly weaker in the Nx-RDNx group. A lucigenin assay of NAD(P)H oxidase activity in isolated glomeruli indicated that renal denervation may have caused the reduction in reactive oxygen species through suppression of the activity of NAD(P)H oxidase. Plasma renin activity was significant increased in the Nx-Sham group compared with DH, and renal denervation suppressed this activity. Conclusions: Renal sympathetic denervation helps protect against glomerular sclerosis, possibly by suppressing NAD(P)H oxidase activity, thereby decreasing glomerular reactive oxygen species.