Published online before print July 21, 2003, doi: 10.1161/01.HYP.0000084634.97353.1A
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(Hypertension. 2003;42:669.)
© 2003 American Heart Association, Inc.
State of the Art Lectures |
Inhibitors of 20-HETE Formation Promote Salt-Sensitive Hypertension in Rats
From the Department of Physiology, Medical College of Wisconsin, Milwaukee.
Correspondence to Richard J. Roman, PhD, Medical College of Wisconsin, Department of Physiology, 8701 Watertown Plank Road, Milwaukee, WI 53226. E-mail rroman{at}mcw.edu
This study examined whether chronic blockade of epoxyeicosatrienoic acids (EETs) and/or 20-hydroxyeicosatetraenoic acid (20-HETE) formation promotes development of salt-sensitive hypertension. Changes in blood pressure, renal cytochrome P450 metabolism of arachidonic acid, and 20-HETE excretion in response to a high salt diet were measured in rats chronically treated with 1-aminobenzotriazole (ABT, 50 mg/kg per day) to block EETs and 20-HETE formation or N-hydroxy-N'-(4-butyl-2 methylphenyl) formamidine (HET0016, 10 mg/kg per day) that selectively reduces 20-HETE formation. ABT reduced blood pressure in rats fed a low salt (0.4% NaCl) diet, but blood pressure rose by 20 mm Hg after these rats were switched to a high salt (8% NaCl) diet for 10 days. HET0016 had no effect on blood pressure in rats fed a low salt diet; however, blood pressure rose by 18 mm Hg after the rats were fed a high salt diet. 20-HETE formation in kidney homogenates rose by 30% and epoxygenase activity doubled when rats were fed a high salt diet. Chronic treatment with ABT and HET0016 inhibited the renal formation of 20-HETE by 
90%. Renal epoxygenase activity decreased by 76% in ABT-treated rats and was not significantly altered in rats treated with HET0016. 20-HETE excretion rose from 470±21 to 570±41 ng/d when the rats were switched from the low to the high salt diet. 20-HETE excretion fell by 68% and 85% in rats that were chronically treated with ABT and HET0016. These results suggest that chronic blockade of the formation of 20-HETE promotes the development of salt-sensitive hypertension in rats.
Key Words: rats, Dahl • metabolism • arachidonic acids • blood pressure • hypertension, sodium-dependent
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