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)
Roman
R J
RJ
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
Ma
Y H
YH
Frohlich
B
B
Markham
B
B
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002994:Clofibrate / Q000494:pharmacology*; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D006973:Hypertension / Q000517:prevention & control*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains; D012965:Sodium Chloride / Q000494:pharmacology
D006893:Hydroxyeicosatetraenoic Acids; D008055:Lipids; D016718:Arachidonic Acid; D012965:Sodium Chloride; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A; D002994:Clofibrate