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 - 2013/9
Y1 - 2013/9
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.
AB - 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.
KW - ω-3 polyunsaturated fatty acids
KW - Angiotensin-Idependent hypertension
KW - DHA
KW - EPA
KW - Soluble epoxide hydrolase inhibitors
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U2 - 10.1097/FJC.0b013e318298e460
DO - 10.1097/FJC.0b013e318298e460
M3 - Article
C2 - 23676336
AN - SCOPUS:84884671223
VL - 62
SP - 285
EP - 297
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
SN - 0160-2446
IS - 3
ER -