Soluble epoxide hydrolase inhibition and peroxisome proliferator activated receptor γ agonist improve vascular function and decrease renal injury in hypertensive obese rats

John D. Imig, Katie A. Walsh, Md Abdul Hye Khan, Tasuku Nagasawa, Mary Cherian-Shaw, Sean M. Shaw, Bruce D. Hammock

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Cardiometabolic syndrome occurs with obesity and consists of pathophysiological factors that increase the risk for cardiovascular events. Soluble epoxide hydrolase inhibition (sEHi) is a novel therapeutic approach that exerts renal and cardiovascular protection. Although sEHi as a therapeutic approach is promising, it could be more effective for the treatment of cardiometabolic syndrome when combined with peroxisome proliferator activated receptor γ (PPARγ) agonists. We hypothesized that the PPARγ agonist, rosiglitazone in combination with a sEHi (tAUCB) will provide synergistic actions to decrease blood pressure, improve vascular function, decrease inflammation, and prevent renal damage in spontaneously hypertensive obese rats (SHROB). SHROB were treated with rosiglitazone, tAUCB or the combination of tAUCB and rosiglitazone for four-weeks and compared with spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Blood pressure increased in SHROB (164 ± 7 mmHg) and decreased 10 mmHg when treated with rosiglitazone, tAUCB, or tAUCB and rosiglitazone. Mesenteric artery dilation to the KATP channel opener pinacidil was attenuated in SHROB (EMax = 77 ± 7%), compared with WKY (EMax = 115 ± 19) and SHR (EMax = 93 ± 12%). Vasodilation to pinacidil was improved by rosiglitazone (EMax = 92 ± 14%) but not tAUCB. Renal macrophage infiltration increased in SHROB and significantly decreased with rosiglitazone or tAUCB and rosiglitazone treatment. Albuminuria was increased in SHROB (90 ± 20 mg/d) and was significantly decreased by the combination of tAUCB and rosiglitazone (37 ± 9 mg/d). Glomerular injury in SHROB was also significantly decreased by tAUCB and rosiglitazone. These results indicate that even though sEHi or PPARγ agonist have benefits when used individually, the combination is more beneficial for the multidisease features in cardiometabolic syndrome.

Original languageEnglish (US)
Pages (from-to)1402-1412
Number of pages11
JournalExperimental Biology and Medicine
Volume237
Issue number12
DOIs
StatePublished - Dec 2012

Fingerprint

rosiglitazone
Epoxide Hydrolases
Peroxisome Proliferator-Activated Receptors
Blood Vessels
Rats
Inbred SHR Rats
Kidney
Wounds and Injuries
Pinacidil
Blood pressure
Blood Pressure
KATP Channels
Albuminuria
Mesenteric Arteries
Inbred WKY Rats

Keywords

  • Epoxyeicosatrienoic acid
  • Kidney
  • Metabolic syndrome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Soluble epoxide hydrolase inhibition and peroxisome proliferator activated receptor γ agonist improve vascular function and decrease renal injury in hypertensive obese rats. / Imig, John D.; Walsh, Katie A.; Khan, Md Abdul Hye; Nagasawa, Tasuku; Cherian-Shaw, Mary; Shaw, Sean M.; Hammock, Bruce D.

In: Experimental Biology and Medicine, Vol. 237, No. 12, 12.2012, p. 1402-1412.

Research output: Contribution to journalArticle

Imig, John D. ; Walsh, Katie A. ; Khan, Md Abdul Hye ; Nagasawa, Tasuku ; Cherian-Shaw, Mary ; Shaw, Sean M. ; Hammock, Bruce D. / Soluble epoxide hydrolase inhibition and peroxisome proliferator activated receptor γ agonist improve vascular function and decrease renal injury in hypertensive obese rats. In: Experimental Biology and Medicine. 2012 ; Vol. 237, No. 12. pp. 1402-1412.
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