Clofibrate Prevents the Development of Hypertension in Dahl Salt-Sensitive Rats.
Roman, Richard J.; Ma, Yunn-Hwa; Frohlich, Bruce; Markham, Bruce
21(6, Part 2):985-988, June 1993.
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We have reported that cytochrome P-450-dependent [omega]-hydroxylatlon 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). These observations are consistent with the hypothesis that a deficiency in the ([omega]-hydroxylation of fatty acids by P-450 in the outer medulla of the kidney may contribute to the resetting kidney function and the development or hypertension in Dahl SS/Jr rats.
(C) 1993 American Heart Association, Inc.