Evolution of liver antioxidant status and iron implication during the development of deoxycorticosterone-saline hypertension in rats.

Hypertension is known to be associated with an oxidative stress resulting from an imbalance of antioxidant defense mechanisms in various tissues. The purpose of this study was to investigate the relationship between the increase of arterial blood pressure, measured during the gradual development of experimental hypertension in deoxycorticosterone (DOCA)-salt-treated rats, and an early imbalance of liver antioxidant status. The levels of liver oxidant/antioxidant markers and iron were studied during the induction of hypertension in 3-, 6-, and 8-wk DOCA-salt-treated Sprague-Dawley rats. Hepatic antioxidant defenses were decreased as early as 3 wk of hypertensive treatment: the decrease of peroxidase-reductase-transferase and catalase activities was associated with a significant increase of thiobarbituric acid reactive substances (TBARS) levels. Liver oxidative stress increased until 6 wk and remained stable at 8 wk of DOCA-salt treatment. Concurrently, liver iron levels were increased at 6 wk and returned to normal values after 8 wk of hypertensive treatment. Iron seems to be an inductor of liver oxidative stress and responsible for the persistent oxidative stress, most likely through secondary free-radical release. Thus, our data (1) confirm that hypertension in DOCA-salt-treated rats might be a free-radical-dependent disease where hepatic oxidant/antioxidant imbalance is obviously involved from the beginning of blood pressure elevation and (2) suggest that the use of suitable iron chelators might reverse liver oxidative stress associated with the increase of blood pressure.

Dietary vitamin C supplementation decreases blood pressure in DOCA-salt hypertensive male Sprague-Dawley rats and this is associated with increased liver oxidative stress.

The effects of a vitamin C supplemented diet on blood pressure, body and liver weights, liver antioxidant status, iron and copper levels were investigated in DOCA-salt treated and untreated Sprague-Dawley (SD) male rats after 8 weeks of treatment. Vitamin C supplementation had no effect on blood pressure in SD rats but induced a significant decrease in blood pressure in DOCA-salt treated rats, the decrease being more efficient at 50 mg/kg of vitamin C than at 500 mg/kg. Hepatic lipid peroxidation and iron levels were significantly increased in DOCA-salt hypertensive rats whereas total hepatic antioxidant capacity (HAC), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were decreased. Vitamin C supplementation did not affect the overall antioxidant defences of control SD rat livers. In contrast, vitamin C supplementation accentuated the DOCA-salt induced accumulation of liver iron and lipid peroxidation. This occurred without any notable aggravation in the antioxidant deficiency of vitamin C supplemented DOCA-salt treated rat livers. Our data suggest that DOCA-salt treatment induces an accumulation of iron in rat livers which is responsible for the prooxidant effect of vitamin C. The normalization of blood pressure in DOCA-salt treated rats by vitamin C supplementation appears thus independent from liver antioxidant status.

Effect of exercise training on liver antioxidant status of deoxycorticosterone acetate salt induced hypertensive rats.

Several animal models have been developed to study the pathogenesis of hypertension. Deoxycorticosterone acetate (DOCA) salt induced hypertensive rats are adrenal models used to mimic human Conn's syndrome. Because previous studies showed a beneficial effect of chronic exercise (swimming) on the development of arterial hypertension in spontaneously hypertensive rats (which appears similar to human essential hypertension), we decided to evaluate the effects of swimming on DOCA-salt induced hypertension and liver antioxidant status. Therefore, the aim of this experiment was to study whether the swim training would improve hypertension and liver antioxidant status in DOCA-salt rats. DOCA-salt rats and control Sprague-Dawley rats were trained to swim 1 h/day, 5 days/week for 6 weeks and were sacrificed 48 h after the last exercise period. Systolic blood pressure was recorded before the sacrifice, and liver antioxidant status was evaluated in hepatic homogenates after the sacrifice. Swim exercise did not decrease systolic blood pressure in control and DOCA-salt rats but induced changes in liver activities of antioxidant enzymes, showing that exercise provoked liver oxidative stress in control and DOCA-salt rats. In comparison with our previous studies using spontaneously hypertensive rats, we conclude that the beneficial effects of chronic exercise on systolic blood pressure in rats are dependent on strain and the type of experimental hypertension.