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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.JC

Abstract

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.

Authors+Show Affiliations

*Department of Entomology and UC Davis Comprehensive Cancer Center, University of California, Davis, CA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23676336

Citation

Ulu, Arzu, et al. "Anti-inflammatory Effects of Ω-3 Polyunsaturated Fatty Acids and Soluble Epoxide Hydrolase Inhibitors in angiotensin-II-dependent Hypertension." Journal of Cardiovascular Pharmacology, vol. 62, no. 3, 2013, pp. 285-97.
Ulu A, Harris TR, Morisseau C, et al. Anti-inflammatory effects of ω-3 polyunsaturated fatty acids and soluble epoxide hydrolase inhibitors in angiotensin-II-dependent hypertension. J Cardiovasc Pharmacol. 2013;62(3):285-97.
Ulu, A., Harris, T. R., Morisseau, C., Miyabe, C., Inoue, H., Schuster, G., Dong, H., Iosif, A. M., Liu, J. Y., Weiss, R. H., Chiamvimonvat, N., Imig, J. D., & Hammock, B. D. (2013). Anti-inflammatory effects of ω-3 polyunsaturated fatty acids and soluble epoxide hydrolase inhibitors in angiotensin-II-dependent hypertension. Journal of Cardiovascular Pharmacology, 62(3), 285-97. https://doi.org/10.1097/FJC.0b013e318298e460
Ulu A, et al. Anti-inflammatory Effects of Ω-3 Polyunsaturated Fatty Acids and Soluble Epoxide Hydrolase Inhibitors in angiotensin-II-dependent Hypertension. J Cardiovasc Pharmacol. 2013;62(3):285-97. PubMed PMID: 23676336.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-inflammatory effects of ω-3 polyunsaturated fatty acids and soluble epoxide hydrolase inhibitors in angiotensin-II-dependent hypertension. AU - Ulu,Arzu, AU - Harris,Todd R, AU - Morisseau,Christophe, AU - Miyabe,Christina, AU - Inoue,Hiromi, AU - Schuster,Gertrud, AU - Dong,Hua, AU - Iosif,Ana-Maria, AU - Liu,Jun-Yan, AU - Weiss,Robert H, AU - Chiamvimonvat,Nipavan, AU - Imig,John D, AU - Hammock,Bruce D, PY - 2013/5/17/entrez PY - 2013/5/17/pubmed PY - 2014/4/17/medline SP - 285 EP - 97 JF - Journal of cardiovascular pharmacology JO - J. Cardiovasc. Pharmacol. VL - 62 IS - 3 N2 - 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. SN - 1533-4023 UR - https://www.unboundmedicine.com/medline/citation/23676336/Anti_inflammatory_effects_of_ω_3_polyunsaturated_fatty_acids_and_soluble_epoxide_hydrolase_inhibitors_in_angiotensin_II_dependent_hypertension_ L2 - http://dx.doi.org/10.1097/FJC.0b013e318298e460 DB - PRIME DP - Unbound Medicine ER -