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

We have reported that cytochrome P-450-dependent omega-hydroxylation of arachidonic acid is reduced in microsomes prepared from the renal outer medulla of Dahl 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 omega-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 (n = 19) SS/Jr rats. Clofibrate had no effect 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 omega-hydroxylation of arachidonic and lauric acids by renal cortical and outer medullary microsomes was greater than that seen in vehicle-treated rats (n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)