Administration of a substituted adamantyl urea inhibitor of soluble epoxide hydrolase protects the kidney from damage in hypertensive Goto-Kakizaki rats

Jeffrey J. Olearczyk, Jeffrey E. Quigley, Bradford C. Mitchell, Tatsuo Yamamoto, In Hae Kim, John W. Newman, Ayala Luria, Bruce D. Hammock, John D. Imig

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Abstract

Hypertension and Type 2 diabetes are co-morbid diseases that lead to the development of nephropathy. sEH (soluble epoxide hydrolase) inhibitors are reported to provide protection from renal injury. We hypothesized that the sEH inhibitor AUDA [12-(3-adamantan-1-yl-ureido)-dodecanoic acid] protects the kidney from the development of nephropathy associated with hypertension and Type 2 diabetes. Hypertension was induced in spontaneously diabetic GK (Goto-Kakizaki) rats using AngII (angiotensin II) and a high-salt diet. Hypertensive GK rats were treated for 2 weeks with either AUDA or its vehicle added to drinking water. MAP (mean arterial pressure) increased from 118 ± 2 mmHg to 182 ± 20 and 187 ± 6 mmHg for vehicle and AUDA-treated hypertensive GK rats respectively. AUDA treatment did not alter blood glucose. Hypertension in GK rats resulted in a 17-fold increase in urinary albumin excretion, which was decreased with AUDA treatment. Renal histological evaluation determined that AUDA treatment decreased glomerular and tubular damage. In addition, AUDA treatment attenuated macrophage infiltration and inhibited urinary excretion of MCP-1 (monocyte chemoattractant protein-1) and kidney cortex MCP-1 gene expression. Taken together, these results provide evidence that sEH inhibition with AUDA attenuates the progression of renal damage associated with hypertension and Type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)61-70
Number of pages10
JournalClinical Science
Volume116
Issue number1
DOIs
StatePublished - Jan 2009

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Epoxide Hydrolases
Urea
Kidney
Hypertension
Type 2 Diabetes Mellitus
Chemokine CCL2
Kidney Cortex
12-(3-adamantan-1-ylureido)dodecanoic acid
Angiotensin II
Drinking Water
Blood Glucose
Albumins
Arterial Pressure
Salts
Macrophages
Diet
Gene Expression
Wounds and Injuries

Keywords

  • Blood pressure
  • Diabetes
  • Eicosanoid
  • Inflammation
  • Nephropathy
  • Soluble epoxide hydrolase

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Olearczyk, J. J., Quigley, J. E., Mitchell, B. C., Yamamoto, T., Kim, I. H., Newman, J. W., ... Imig, J. D. (2009). Administration of a substituted adamantyl urea inhibitor of soluble epoxide hydrolase protects the kidney from damage in hypertensive Goto-Kakizaki rats. Clinical Science, 116(1), 61-70. https://doi.org/10.1042/CS20080039

Administration of a substituted adamantyl urea inhibitor of soluble epoxide hydrolase protects the kidney from damage in hypertensive Goto-Kakizaki rats. / Olearczyk, Jeffrey J.; Quigley, Jeffrey E.; Mitchell, Bradford C.; Yamamoto, Tatsuo; Kim, In Hae; Newman, John W.; Luria, Ayala; Hammock, Bruce D.; Imig, John D.

In: Clinical Science, Vol. 116, No. 1, 01.2009, p. 61-70.

Research output: Contribution to journalArticle

Olearczyk, JJ, Quigley, JE, Mitchell, BC, Yamamoto, T, Kim, IH, Newman, JW, Luria, A, Hammock, BD & Imig, JD 2009, 'Administration of a substituted adamantyl urea inhibitor of soluble epoxide hydrolase protects the kidney from damage in hypertensive Goto-Kakizaki rats', Clinical Science, vol. 116, no. 1, pp. 61-70. https://doi.org/10.1042/CS20080039
Olearczyk, Jeffrey J. ; Quigley, Jeffrey E. ; Mitchell, Bradford C. ; Yamamoto, Tatsuo ; Kim, In Hae ; Newman, John W. ; Luria, Ayala ; Hammock, Bruce D. ; Imig, John D. / Administration of a substituted adamantyl urea inhibitor of soluble epoxide hydrolase protects the kidney from damage in hypertensive Goto-Kakizaki rats. In: Clinical Science. 2009 ; Vol. 116, No. 1. pp. 61-70.
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