Renal denervation reduces sympathetic overactivation, brain oxidative stress, and renal injury in rats with renovascular hypertension independent of its effects on reducing blood pressure.

The underlying mechanisms by which renal denervation (RD) decreases blood pressure (BP) remain incompletely understood. In this study, we investigated the effects of ischemic kidney denervation on different sympathetic outflows, brain and renal expression of angiotensin-II receptors, oxidative stress and renal function markers in the 2-kidney, 1-clip (2K-1C) rat model. Surgical RD was performed in Wistar male rats 4-5 weeks after clip implantation. After 10 days of RD, BP, and the activity of sympathetic nerves projecting to the contralateral kidney (rSNA) and splanchnic region were partially reduced in 2K-1C rats, with no change in systemic renin-angiotensin system (RAS). To distinguish the effects of RD from the reduction in BP, 2K-1C rats were treated with hydralazine by oral gavage (25 mg/kg/day for 1 week). RD, but not hydralazine, normalized oxidative stress in the sympathetic premotor brain regions and improved intrarenal RAS, renal injury, and proteinuria. Furthermore, different mechanisms led to renal injury and oxidative stress in the ischemic and contralateral kidneys of 2K-1C rats. Injury and oxidative stress in the ischemic kidney were driven by the renal nerves. Although RD attenuated rSNA, injury and oxidative stress persisted in the contralateral kidney, probably due to increased BP. Therefore, nerves from the ischemic kidney at least partially contribute to the increase in BP, sympathetic outflows, brain oxidative stress, and renal alterations in rats with renovascular hypertension. Based on these findings, the reduction in oxidative stress in the brain is a central mechanism that contributes to the effects of RD on Goldblatt hypertension.