The main cause of death among patients with malignant hypertension is a kidney failure. The promising field in essential and malignant hypertension therapy could be centered on the amelioration of oxidative stress using antioxidant molecules like resveratrol. Resveratrol is a potent antioxidative agent naturally occurred in many plants that possess health-promoting properties. In the present study, we investigated the therapeutic potential of resveratrol, a polyphenol with anti-oxidative activity, in N^G-L-Arginine Methyl Ester (L-NAME) treated spontaneously hypertensive rats (SHR) - malignantly hypertensive rats (MHR). Resveratrol significantly improves oxidative damages by modulation of antioxidant enzymes and suppression of prooxidant factors in the kidney tissue of MHR. Enhanced antioxidant defense in the kidney improves renal function and ameliorates the morphological changes in this target organ. Besides, protective properties of resveratrol are followed by the restoration of the nitrogen oxide (NO) pathway. 4) Conclusion: Antioxidant therapy with resveratrol could represent promising therapeutical approach in hypertension, especially malignant, against kidney damage.

Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v.) twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day), tempol (T,100 mg/kg/day) or combined T+L treatment (by gavage) during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1) protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4) protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2) protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria), pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression. Losartan improved blood pressure, as well as tubular injury and restored anti-inflammatory defense by reverting kNox2 expression to the control level. Interestingly, tempol was more successful in reducing systemic oxidative stress, proteinuria, kMMP-1 and glomerulosclerosis. However, combined treatment failed to overcome the beneficial effects of single treatments in slowing down the progression of ADR-induced nephropathy in SHR.

Oxidative stress has been considered as a central aggravating factor in the development of postischemic acute kidney injury (AKI). The aim of this study was to perform the immunohistochemical analysis of 4-hydroxynonenal (4-HNE), neutrophil gelatinase-associated lipocalin (NGAL), and heme oxygenase-1 (HO-1) tissue expression after apocynin (APO) treatment and hyperbaric oxygenation (HBO) preconditioning, applied as single or combined protocol, in postischemic acute kidney injury induced in spontaneously hypertensive rats (SHR). Twenty-four hours before AKI induction, HBO preconditioning was carried out by exposing to pure oxygen (2.026 bar) twice a day, for 60 min in two consecutive days. Acute kidney injury was induced by removal of the right kidney while the left renal artery was occluded for 45 min by atraumatic clamp. Apocynin was applied in a dose of 40 mg/kg body weight, intravenously, 5 min before reperfusion. We showed increased 4-HNE renal expression in postischemic AKI compared to Sham-operated (SHAM) group. Apocynin treatment, with or without HBO preconditioning, improved creatinine and phosphate clearances, in postischemic AKI. This improvement in renal function was accompanied with decreased 4-HNE, while HO-1 kidney expression restored close to the control group level. NGAL renal expression was also decreased after apocynin treatment, and HBO preconditioning, with or without APO treatment. Considering our results, we can say that 4-HNE tissue expression can be used as a marker of oxidative stress in postischemic AKI. On the other hand, apocynin treatment and HBO preconditioning reduced oxidative damage, and this protective effect might be expected even in experimental hypertensive condition.

Renal ischemia/reperfusion injury is a common cause of acute kidney injury (AKI) and hypertension might contribute to the increased incidence of AKI. The purpose of this study was to investigate the effects of single and combined hyperbaric oxygen (HBO) preconditioning and NADPH oxidase inhibition on oxidative stress, kidney function and structure in spontaneously hypertensive rats (SHR) after renal ischemia reperfusion injury. HBO preconditioning was performed by exposing to pure oxygen (2.026 bar) twice a day for two consecutive days for 60 minutes, and 24h before AKI induction. For AKI induction, the right kidney was removed and ischemia was performed by clamping the left renal artery for 45 minutes. NADPH oxidase inhibition was induced by apocynin (40 mg/kg b.m., intravenously) 5 minutes before reperfusion. AKI significantly increased renal vascular resistance and reduced renal blood flow, which were significantly improved after apocynin treatment. Also, HBO preconditioning, with or without apocynin treatment showed improvement on renal hemodynamics. AKI significantly increased plasma creatinine, urea, phosphate levels and lipid peroxidation in plasma. Remarkable improvement, with decrease in creatinine, urea and phosphate levels was observed in all treated groups. HBO preconditioning, solitary or with apocynin treatment decreased lipid peroxidation in plasma caused by AKI induction. Also, combined with apocynin, it increased catalase activity and solitary, glutathione reductase enzyme activity in erythrocytes. While AKI induction significantly increased plasma KIM– 1 levels, HBO preconditioning, solitary or with apocynin decreased its levels. Considering renal morphology, significant morphological alterations present after AKI induction were significantly improved in all treated groups with reduced tubular dilatation, tubular necrosis in the cortico-medullary zone and PAS positive cast formation. Our results reveal that NADPH oxidase inhibition and hyperbaric oxygen preconditioning, with or without NADPH oxidase inhibition may have beneficial effects, but their protective role should be evaluated in further studies.