Prevention of hypertension and renal dysfunction in Dahl rats by alpha-tocopherol

Although hypertension is a risk factor for the development of end-stage renal disease, not all hypertensive patients progress to develop renal dysfunction. The mechanisms underlying hypertensive nephropathy are poorly understood. The authors have recently shown that the development of hypertension and renal dysfunction is accompanied by an accumulation of partially reduced oxygen and its derivatives, known collectively as reactive oxygen species. In the present study, the effect of a lipid-soluble antioxidant on the development of salt-dependent hypertensive nephropathy was evaluated in the Dahl rat. It was found that a high-salt diet (8% NaCl) led to the development of hypertension, increased renal oxidative stress (superoxide production and 8-epi-prostaglandin F2alpha), and decreased glomerular filtration rate and renal plasma flow in the Dahl salt-sensitive (DSS) rat, and that these adverse effects of salt were prevented by supplementing the high-salt diet with 1000 U/kg chow of alpha-tocopherol. It is well known that urinary cyclic guanosine monophosphate (cGMP) levels are lower in hypertensive DSS rats than in Dahl salt-resistant (DSR) rats on a high-salt diet. Most surprisingly, when supplemented with alpha-tocopherol, DSS rats on an 8% NaCl diet were able to excrete as much cGMP as DSR rats. Taken together, these findings suggest that, in the DSS rat, salt-dependent hypertensive nephropathy and decreased nitric oxide bioavailability are associated with increased oxidative stress, and that antioxidants can preclude these adverse effects of salt feeding, and consequently, prevent salt-dependent hypertension and nephropathy.