Soluble epoxide hydrolase inhibition lowers arterial blood pressure in angiotensin II hypertension

John D. Imig, Xueying Zhao, Jorge H. Capdevila, Christophe Morisseau, Bruce D. Hammock

Research output: Contribution to journalArticle

301 Citations (Scopus)

Abstract

Epoxyeicosatrienoic acids (EETs) have antihypertensive properties and play a part in the maintenance of renal microvascular function. A novel approach to increase EET levels is to inhibit epoxide hydrolase enzymes that are responsible for conversion of biologically active EETs to dihydroxyeicosatrienoic acids (DHETs) that are void of effects on the preglomerular vasculature. We hypothesized that inhibition of soluble epoxide hydrolase (sEH) would lower blood pressure in angiotensin II (Ang II) hypertension. Rat renal cortical tissue was harvested and urine collected 2 weeks following implantation of an osmotic minipump containing Ang II (60 ng/min). Renal cortical sEH protein expression was significantly higher in Ang II hypertension compared with normotensive animals. Likewise, urinary 14,15-DHET levels were significantly increased in hypertensive compared with normotensive animals and averaged 8.1±1.3 and 2.7±1.1 ng/d; respectively. In additional experiments, the sEH inhibitor N-cyclohexyl-N-dodecyl urea (NCND; 3 mg/d) or vehicle (corn oil, 0.5 mL) was administered daily by intraperitoneal injection starting on day 10. Administration of NCND for 4 days lowered systolic blood pressure by 30 mm Hg in Ang II hypertensive animals, whereas the corn oil vehicle had no effect on blood pressure in normotensive or Ang II hypertensive animals. Measurement of blood pressure by indwelling arterial catheters in conscious animals with free movement in their cages confirmed that NCND had antihypertensive properties. Arterial blood pressure averaged 119±5 mm Hg in normotensive, 170±3 mm Hg in hypertensive and 149±10 mm Hg in NCND-treated, Ang II-infused animals. Administration of the potential metabolite of NCND, N-cyclohexylformamide to Ang II hypertensive rats did not lower the systolic blood pressure. These studies demonstrate that increased sEH expression in the Ang II hypertensive kidney leads to increased EET hydration. Moreover, sEH plays a role in the regulation of blood pressure, and inhibition of sEH during Ang II hypertension is antihypertensive.

Original languageEnglish (US)
Pages (from-to)690-694
Number of pages5
JournalHypertension
Volume39
Issue number2 II
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Epoxide Hydrolases
Angiotensin II
Arterial Pressure
Hypertension
Blood Pressure
Antihypertensive Agents
Kidney
Corn Oil
Acids
Indwelling Catheters
Intraperitoneal Injections
Urea
Maintenance
Urine

Keywords

  • Cytochrome P450
  • Endothelium-derived factors
  • Kidney
  • Microcirculation
  • Renal blood flow

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Imig, J. D., Zhao, X., Capdevila, J. H., Morisseau, C., & Hammock, B. D. (2002). Soluble epoxide hydrolase inhibition lowers arterial blood pressure in angiotensin II hypertension. Hypertension, 39(2 II), 690-694. https://doi.org/10.1161/hy0202.103788

Soluble epoxide hydrolase inhibition lowers arterial blood pressure in angiotensin II hypertension. / Imig, John D.; Zhao, Xueying; Capdevila, Jorge H.; Morisseau, Christophe; Hammock, Bruce D.

In: Hypertension, Vol. 39, No. 2 II, 2002, p. 690-694.

Research output: Contribution to journalArticle

Imig, JD, Zhao, X, Capdevila, JH, Morisseau, C & Hammock, BD 2002, 'Soluble epoxide hydrolase inhibition lowers arterial blood pressure in angiotensin II hypertension', Hypertension, vol. 39, no. 2 II, pp. 690-694. https://doi.org/10.1161/hy0202.103788
Imig, John D. ; Zhao, Xueying ; Capdevila, Jorge H. ; Morisseau, Christophe ; Hammock, Bruce D. / Soluble epoxide hydrolase inhibition lowers arterial blood pressure in angiotensin II hypertension. In: Hypertension. 2002 ; Vol. 39, No. 2 II. pp. 690-694.
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