Clofibrate prevents the development of hypertension in dahl salt-sensitive rats

We have reported that cytochrome P-450-depen dent to-hydroxyl at) on of arachfdonic acid is reduced in microsome prepared from the renal outer medulla or Dabi salt-sensitive (SS/Jr) rats, but the functional significance of this observation is unknown. The present study examined whether long-term induction of renal fatty acid to-hydroxylase with clofibrate would alter the development of hypertension in Dahl SS/Jr rats. Dahl SS/Jr rats were placed on a high salt diet (8.0% NaCl) and given either vehicle or clofibrate (80 mg/day) in their drinking water. After 4 weeks of a high salt diet, mean arterial pressure averaged 170±3 mm Hg in vehicle-treated (n=17) and 127±2 mm Hg in clofibrate-treated («=19) SS/Jr rats. Clofibrate had no efTect on arterial pressure in Dahl salt-resistant rats. The antihypertensive effect of clofibrate was reversible. Mean arterial pressure rose from 131 ±4 to 182±8 mm Hg in the first week after clofibrate treatment (n=6) was discontinued. Clofibrate had no effect on arterial pressure in SS/Jr rats (n=9) in which hypertension was already established by feeding the rats a high salt diet for 4 weeks before the study. In clofibrate-treated SS/Jr rats (n=12), the ai-hydroxylation of arachldonic and lauric acids by renal cortical and outer medullary microsomes was greater than that seen in vehicle-treated rats (n=9). These observations are consistent with the hypothesis that a deficiency in the to-hydroxy]ation of fatty acids by P-450 in the outer medulla of the kidney may contribute to the resetting kidney function and the development of hypertension in Dahl SS/Jr rats. (Hypertension 1993;21:985-988)