Faculty Collaboration Database

An orally active epoxide hydrolase inhibitor lowers blood pressure and provides renal protection in salt-sensitive hypertension. Hypertension 2005 Oct;46(4):975-81

Date

09/15/2005

Pubmed ID

16157792

Pubmed Central ID

PMC1444888

DOI

10.1161/01.HYP.0000176237.74820.75

Scopus ID

2-s2.0-33644654633 (requires institutional sign-in at Scopus site)   228 Citations

Abstract

The present study tested the hypothesis that increasing epoxyeicosatrienoic acids by inhibition of soluble epoxide hydrolase (sEH) would lower blood pressure and ameliorate renal damage in salt-sensitive hypertension. Rats were infused with angiotensin and fed a normal-salt diet or an 8% NaCl diet for 14 days. The sEH inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), was given orally to angiotensin-infused animals during the 14-day period. Plasma AUDA metabolite levels were measured, and they averaged 10+/-2 ng/mL in normal-salt angiotensin hypertension and 19+/-3 ng/mL in high-salt angiotensin hypertension on day 14 in the animals administered the sEH inhibitor. Mean arterial blood pressure averaged 161+/-4 mm Hg in normal-salt and 172+/-5 mm Hg in the high-salt angiotensin hypertension groups on day 14. EH inhibitor treatment significantly lowered blood pressure to 140+/-5 mm Hg in the normal-salt angiotensin hypertension group and to 151+/-6 mm Hg in the high-salt angiotensin hypertension group on day 14. The lower arterial blood pressures in the AUDA-treated groups were associated with increased urinary epoxide-to-diol ratios. Urinary microalbumin levels were measured, and ED-1 staining was used to determine renal damage and macrophage infiltration in the groups. Two weeks of AUDA treatment decreased urinary microalbumin excretion in the normal-salt and high-salt angiotensin hypertension groups and macrophage number in the high-salt angiotensin hypertension group. These data demonstrate that sEH inhibition lowers blood pressure and ameliorates renal damage in angiotensin-dependent, salt-sensitive hypertension.

Author List

Imig JD, Zhao X, Zaharis CZ, Olearczyk JJ, Pollock DM, Newman JW, Kim IH, Watanabe T, Hammock BD

MESH terms used to index this publication - Major topics in bold

Adamantane
Albuminuria
Angiotensins
Animals
Blood Pressure
Cell Count
Epoxide Hydrolases
Hypertension
Kidney
Kidney Diseases
Lauric Acids
Macrophages
Male
Rats
Rats, Sprague-Dawley
Sodium Chloride