Effect of Antioxidants on Salt-Induced Hypertension and Renal Dysfunction.

Abstract

43 We have demonstrated that the development of salt-dependent hypertension and renal dysfunction in the Dahl salt-sensitive (DSS) rat is accompanied by the accumulation of reactive oxygen species (ROS). To determine whether oxidative stress contributes to the development of progressive renal dysfunction, we examined the effect of dietary vitamin E, a natural antioxidant, on a model of salt-dependent hypertension. Dahl salt-resistant (DSR) and DSS rats were kept on 8% NaCl (HS) or 8% NaCl + 1000 U./kg chow of vitamin E (HSE) for 2 weeks. During this time blood pressure was monitored using the tail plethismography method. After 14 days on the diets, DSS rats on HS diet were hypertensive, as compared to the DSR rats (171.3 ± 7.4 vs. 138.4 ± 2.4 mmHg; p<0.0001), whereas the animals on the HSE diet remained normotensive (125.1 ± 3.7 vs. 114.0 ± 5.4 mmHg). The animals were then instrumented for the evaluation of renal function, measured as clearance of para-aminohippuric acid (Cl PAH ) and clearance of inulin (Cl In ). As a measure of oxidative stress, kidney and blood samples were harvested for the determination of superoxide production and plasma 8-isoprostanes (8-IP), respectively. Results show that hypertensive DSS rats appear to have lower Cl PAH and Cl In , greater renal superoxide production, and greater plasma 8-IP concentration than the normotensive DSR rats (Cl PAH : 1.93 ± 0.15 vs. 4.11 ± 0.5 ml/min, p<0.005; Cl In : 1.21 ± 0.19 vs. 2.05 ± 0.60 ml/min., p<0.01; O - 2 : 664 ± 33 vs. 374 ± 13 nmol/mg protein/min, p<0.05; and 8-IP: 1494.3 ± 93.4 vs. 386.6 ± 30.0 pM, p<0.001). However, when DSR and DSS rats were kept on the HSE diet, no differences were observed (Cl PAH : 3.31 ± 0.34 vs. 3.29 ± 0.45 ml/min; Cl In : 1.89 ± 0.16 vs. 2.03 ± 0.08 ml/min.; O - 2 : 372 ± 10 vs. 344 ± 23 nmol/mg protein/min; and 8-IP: 276.1 ± 33.2 vs. 278.5 ± 28.3 pM). These results suggest that the incremental production of ROS during salt feeding in DSS rats plays a role in the development of hypertension and renal dysfunction in this model, and that the lipid-soluble antioxidant vitamin E can attenuate the production of ROS and prevent salt-induced hypertension and renal dysfunction.