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)