Anti-inflammatory effects of ω-3 polyunsaturated fatty acids and soluble epoxide hydrolase inhibitors in angiotensin-II-dependent hypertension. J Cardiovasc Pharmacol 2013 Sep;62(3):285-97
Date
05/17/2013Pubmed ID
23676336Pubmed Central ID
PMC3773051DOI
10.1097/FJC.0b013e318298e460Scopus ID
2-s2.0-84884671223 (requires institutional sign-in at Scopus site) 90 CitationsAbstract
The mechanisms underlying the anti-inflammatory and antihypertensive effects of long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFAs) are still unclear. The epoxides of an ω-6 fatty acid, arachidonic acid epoxyeicosatrienoic acids also exhibit antihypertensive and anti-inflammatory effects. Thus, we hypothesized that the major ω-3 PUFAs, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may lower the blood pressure and attenuate renal markers of inflammation through their epoxide metabolites. Here, we supplemented mice with an ω-3 rich diet for 3 weeks in a murine model of angiotensin-II-dependent hypertension. Also, because EPA and DHA epoxides are metabolized by soluble epoxide hydrolase (sEH), we tested the combination of an sEH inhibitor and the ω-3 rich diet. Our results show that ω-3 rich diet in combination with the sEH inhibitor lowered Ang-II, increased the blood pressure, further increased the renal levels of EPA and DHA epoxides, reduced renal markers of inflammation (ie, prostaglandins and MCP-1), downregulated an epithelial sodium channel, and upregulated angiotensin-converting enzyme-2 message and significantly modulated cyclooxygenase and lipoxygenase metabolic pathways. Overall, our findings suggest that epoxides of the ω-3 PUFAs contribute to lowering systolic blood pressure and attenuating inflammation in part by reduced prostaglandins and MCP-1 and by upregulation of angiotensin-converting enzyme-2 in angiotensin-II-dependent hypertension.
Author List
Ulu A, Harris TR, Morisseau C, Miyabe C, Inoue H, Schuster G, Dong H, Iosif AM, Liu JY, Weiss RH, Chiamvimonvat N, Imig JD, Hammock BDMESH terms used to index this publication - Major topics in bold
Angiotensin IIAnimals
Anti-Inflammatory Agents, Non-Steroidal
Antihypertensive Agents
Combined Modality Therapy
Dietary Supplements
Disease Models, Animal
Enzyme Inhibitors
Epithelial Sodium Channel Blockers
Epithelial Sodium Channels
Epoxide Hydrolases
Fatty Acids, Omega-3
Hypertension, Renal
Inflammation Mediators
Kidney
Lipid Peroxidation
Male
Mice
Mice, Inbred Strains
Peptidyl-Dipeptidase A
Random Allocation
Solubility