Role of Oxidative Stress in the Neural Control of Intra-Renal Hemodynamics in Stroke-Prone Spontaneously Hypertensive Rats

TL;DR

This study explores how oxidative stress affects kidney blood flow in rats prone to hypertension and stroke, and how nerve stimulation and antioxidants influence this.

Contribution

The study reveals a novel protective mechanism involving hydrogen peroxide and superoxide anion in renal hemodynamic regulation under oxidative stress.

Findings

Renal nerve stimulation reduced blood perfusion in both the cortex and medulla of SHRSP rats.

Co-infusion of tempol and catalase mitigated the perfusion reduction, suggesting a role for hydrogen peroxide.

DETC also reduced perfusion decline, indicating a novel protective mechanism.

Abstract

Excessive oxidative stress within the renal medulla is implicated in the development of hypertension, potentially modulated by renal nerve stimulation (RNS). This study examined the effects of RNS on cortical and medullary blood perfusion in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP) under both normal conditions and at varying levels of oxidative stress. Male SHRSP rats were assigned to five experimental groups and subjected to RNS at different frequencies, with infusions of vehicle, tempol, tempol plus catalase (tem + cat), diethyldithiocarbamic acid (DETC), or L-nitro-arginine methyl ester (L-NAME) at the renal cortico-medullary border (CMB). Regional blood perfusion of the renal cortex and medulla (CBP and MBP, respectively) was assessed using Laser-Doppler flowmetry. RNS significantly reduced CBP and MBP by 43 ± 8% and 23 ± 4%, respectively, at 8 Hz. Co-infusion of tempol plus catalase significantly attenuated the RNS-induced reductions in both CBP and MBP. Similarly, DETC infusion mitigated RNS-induced decreases in CBP and MBP. In contrast, tempol alone and L-NAME did not protect against the RNS-induced under-perfusion of the renal cortex and medulla. The results suggest that simultaneous removal of superoxide anion and hydrogen peroxide (H2O2) can alleviate the reduction in renal blood perfusion caused by RNS, emphasizing a crucial role for H2O2 in renal hemodynamic regulation. Interestingly, DETC, which is expected to elevate superoxide anion levels, also mitigated RNS-induced under-perfusion, suggesting the presence of a potentially novel indirect protective mechanism that warrants further investigation.

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