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Soluble epoxide hydrolase inhibition and peroxisome proliferator activated receptor γ agonist improve vascular
John D Imig1, Katie A Walsh, Md Abdul Hye Khan
1Department of Pharmacology & Toxicology and Cardiovascular Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. jdimig@mcw.edu
Experimental Biology and Medicine (Maywood, N.J.)
|January 29, 2013
Summary
Combining soluble epoxide hydrolase inhibition (sEHi) with rosiglitazone, a PPARγ agonist, offers superior benefits for cardiometabolic syndrome. This combination effectively reduces blood pressure, inflammation, and renal damage in obese rats.
Area of Science:
- Cardiovascular Science
- Nephrology
- Endocrinology
Background:
- Cardiometabolic syndrome, linked to obesity, elevates cardiovascular event risk through multiple pathophysiological factors.
- Soluble epoxide hydrolase inhibition (sEHi) shows promise for renal and cardiovascular protection.
- Combining sEHi with peroxisome proliferator activated receptor γ (PPARγ) agonists may enhance cardiometabolic syndrome treatment.
Purpose of the Study:
- To investigate the synergistic effects of rosiglitazone (a PPARγ agonist) and tAUCB (a sEHi) on blood pressure, vascular function, inflammation, and renal damage.
- To evaluate the combination therapy's efficacy in spontaneously hypertensive obese rats (SHROB) model of cardiometabolic syndrome.
Main Methods:
- SHROB rats were treated for four weeks with rosiglitazone, tAUCB, or a combination of both.
- Control groups included spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats.
- Measurements included blood pressure, mesenteric artery vasodilation, renal macrophage infiltration, albuminuria, and glomerular injury.
Main Results:
- The combination therapy significantly decreased blood pressure, improved vascular function, and reduced renal macrophage infiltration compared to individual treatments.
- Albuminuria and glomerular injury were notably reduced by the combined administration of tAUCB and rosiglitazone.
- While rosiglitazone improved vasodilation, the combination therapy demonstrated broader benefits across multiple cardiometabolic syndrome features.
Conclusions:
- The combination of sEHi (tAUCB) and PPARγ agonist (rosiglitazone) exhibits synergistic effects in ameliorating key features of cardiometabolic syndrome.
- This combined therapeutic approach provides superior renal and cardiovascular protection compared to individual agents in the SHROB model.
- The findings support the potential of combining sEHi and PPARγ agonists as a novel strategy for managing cardiometabolic syndrome.
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