Oxidative Stress and Antioxidant Treatment in Hypertension and the Associated Renal Damage

Abstract

Reactive oxygen species (ROS) are elevated in humans with hypertension many of which develop end-stage renal disease (ESRD), and antioxidant capacity is decreased. About one-half of essential hypertensives have a salt-sensitive type of hypertension, and the amount of renal damage that occurs in salt-sensitive hypertensives greatly exceeds that of non-salt-sensitive hypertensives. Antioxidant therapy can improve cardiovascular outcomes in humans but only if sufficient doses are used. Salt-sensitive hypertensive animal models, especially Dahl salt-sensitive rats, have been used to investigate the relationship between hypertension, ROS and end-stage renal damage. In experimental salt-sensitive hypertension, ROS increase and significant renal damage occur. In the Dahl salt-sensitive (S) rat on high Na for 3 weeks, renal damage is mild, renal levels of superoxide dismutase are decreased, and treatment with Tempol reduces arterial pressure. In the Dahl S rat on high Na for 5 weeks, renal damage is severe, GFR and renal plasma flow are decreased, and renal superoxide production is high. Treatment with vitamins C and E decreases renal superoxide production and renal damage and prevents the decrease in renal hemodynamics. Antioxidant treatment reduces arterial pressure, aortic superoxide production and renal inflammation in DOCA-salt rats, and decreases blood pressure and aortic superoxide release and increases bioactive nitric oxide in SHR stroke-prone rats. In conclusion, in both human and experimental salt-sensitive hypertension, superoxide production and renal damage are increased, antioxidant capacity is decreased, and antioxidant therapy can be helpful.

Ablation of the gene encoding p66Shc protects mice against AGE-induced glomerulopathy by preventing oxidant-dependent tissue injury and further AGE accumulation

“…Conversely, ROS-independent effects do not appear to contribute significantly to AGE-induced renal tissue injury. This observation is in agreement with previous studies, indicating that interventions aimed at reducing oxidative stress are effective in preventing different types of experimental renal disease [43][44][45][46] and that amelioration of diabetic and nondiabetic renal and cardiovascular disease observed in the p66 Shc KO mouse model is associated with reduction of oxidative stress [34][35][36][37][38].…”

High intensity interval training favourably affects antioxidant and inflammation mRNA expression in early-stage chronic kidney disease

“…In the present study, significant HIITrelated increases in the mRNA expression of Sod1 (compared to SED) and Cat (compared to SED and LIT) may further explain the non-significant differences in post-intervention SBP in HIIT, via eAO-mediated increases in molecular-level protection [10,35]. Research indicates that radical-mediated damage is a primary contributor to the development of hypertension [36] as superoxide can stimulate NFκB transcription factors that eventually lead to endothelial dysfunction and reduced vasodilation, resulting in increased peripheral resistance and elevated blood pressure [37].…”

Redox Control of Renal Function and Hypertension

“…Dobrian et al (55, 228) demonstrated that salt loading leads to hypertension via NAD(P)H-dependent mechanisms that can also exacerbate renal injury and proteinuria in obese spontaneously hypertensive rats. Salt loading has also been shown to increase oxidative stress and blood pressure when the animals are treated for longer intervals and to induce p47 phox and gp91 phox in rat kidney cortices (201). Proposed mechanisms include paradoxic mineralocorticoid receptor (MR) activation of NAD(P)H oxidase and oxidative stress.…”