Impact of Total or Afferent Renal-Nerve Denervation on Cardiovascular and Renal Function in Sprague Dawley Rats Fed High-Fructose and High-Sodium Diet.

Background: Combined high fructose and high sodium diet (FHS) is linked to elevated blood pressure (BP), heightened sympathetic activity, and cardiovascular and renal dysfunction. Total-renal denervation is effective in lowering BP in some hypertension models. Objectives: The present studies tested whether selective afferent (A-RDNx) or total-renal denervation (T-RDNx) ameliorates FHS cardiovascular and renal function. Methods: Male and female Sprague Dawley rats were fed 20% glucose and 0.4% Na chow for one week then assigned to one of four groups: 20% glucose plus 0.4% Na sham-operation (G-Sham) or 20% fructose plus 4% Na with either sham-operation (F-Sham), A-RDNx, or T-RDNx for ~21 days. Telemetric BP and heart rate, echocardiography, pulse-wave velocity (PWV), and renal function were assessed. Results: T-RDNx reduced FHS-induced high BP in both sexes. LVEF did not differ, but global longitudinal strain showed hypercontractility in male F-Sham, which normalized with A-RDNx or T-RDNx. Increased LV perivascular fibrosis in F-Sham rats of both sexes was prevented by A-RDNx or T-RDNx. T-RDNx improved elevated PWV, endothelium-independent vasodilation by myography, and aortic oxidative stress in male F-Sham aortas. High plasma renin activity in male F-Sham decreased with T-RDNx to levels similar to G-Sham rats. Serum creatinine, urine albumin:creatinine ratio, and mesangial hypercellularity in F-Sham male rats decreased with A-RDNx or T-RDNx. Renal function was unchanged in female F-Sham; T-RDNx decreased albuminuria. Conclusions: Renal-sympathetic nerves play a crucial role in elevated BP, cardiac dysfunction, vascular stiffness, and renal impairment associated with FHS diet, particularly in male rats, and implicates a complex interplay with BP, the renin-angiotensin system, and oxidative stress.