Abstract
Mediators of antihypertensive actions of docosahexaenoic acid (DHA) are largely unknown. The omega-3 epoxide of DHA, 19, 20-EDP (epoxy docosapentaenoic acid), is metabolized by soluble epoxide hydrolase (sEH), which also metabolizes the anti-inflammatory and antihypertensive arachidonic acid epoxides, epoxyeicosatrienoic acids (EETs). Based in part on plasma levels of EDPs after a DHA-rich diet, we hypothesized that 19, 20-EDP contributes to the antihypertensive actions of DHA in angiotensin-II (Ang-II)-dependent hypertension. Treatment individually with 19, 20-EDP and a potent sEH inhibitor TPPU (1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea) significantly lowered blood pressure (BP) as compared with Ang-II-infused animals. The largest reduction in BP was obtained with the combination of 19, 20-EDP and TPPU, which was more efficacious than the combination of 14, 15-EET and TPPU. Oxylipin profiling revealed that 19, 20-EDP and 14, 15-EET infusion affected not only most metabolites of the P450 pathway but also renal levels of prostaglandin-E2. Our findings suggest that 19, 20-EDP is a mediator of the antihypertensive effects of DHA in Ang-II-dependent hypertension. It seems that 19, 20-EDP requires metabolic stabilization with a sEH inhibitor to be most effective in lowering BP, although both TPPU and 19, 20-EDP are so effective on their own that demonstrating additive or synergistic interactions is difficult.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 87-99 |
| Number of pages | 13 |
| Journal | Journal of Cardiovascular Pharmacology |
| Volume | 64 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2014 |
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Keywords
- 19,20-epoxy docosapentaenoic acid
- angiotensin- II'dependent hypertension
- docosahexaenoic acid
- omega-3 polyunsaturated fatty acids
- soluble epoxide hydrolase inhibitors
ASJC Scopus subject areas
- Pharmacology
- Cardiology and Cardiovascular Medicine
Cite this
An omega-3 epoxide of docosahexaenoic acid lowers blood pressure in angiotensin-II-dependent hypertension. / Ulu, Arzu; Stephen Lee, Kin Sing; Miyabe, Christina; Yang, Jun; Hammock, Bruce G.; Dong, Hua; Hammock, Bruce D.
In: Journal of Cardiovascular Pharmacology, Vol. 64, No. 1, 2014, p. 87-99.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - An omega-3 epoxide of docosahexaenoic acid lowers blood pressure in angiotensin-II-dependent hypertension
AU - Ulu, Arzu
AU - Stephen Lee, Kin Sing
AU - Miyabe, Christina
AU - Yang, Jun
AU - Hammock, Bruce G.
AU - Dong, Hua
AU - Hammock, Bruce D.
PY - 2014
Y1 - 2014
N2 - Mediators of antihypertensive actions of docosahexaenoic acid (DHA) are largely unknown. The omega-3 epoxide of DHA, 19, 20-EDP (epoxy docosapentaenoic acid), is metabolized by soluble epoxide hydrolase (sEH), which also metabolizes the anti-inflammatory and antihypertensive arachidonic acid epoxides, epoxyeicosatrienoic acids (EETs). Based in part on plasma levels of EDPs after a DHA-rich diet, we hypothesized that 19, 20-EDP contributes to the antihypertensive actions of DHA in angiotensin-II (Ang-II)-dependent hypertension. Treatment individually with 19, 20-EDP and a potent sEH inhibitor TPPU (1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea) significantly lowered blood pressure (BP) as compared with Ang-II-infused animals. The largest reduction in BP was obtained with the combination of 19, 20-EDP and TPPU, which was more efficacious than the combination of 14, 15-EET and TPPU. Oxylipin profiling revealed that 19, 20-EDP and 14, 15-EET infusion affected not only most metabolites of the P450 pathway but also renal levels of prostaglandin-E2. Our findings suggest that 19, 20-EDP is a mediator of the antihypertensive effects of DHA in Ang-II-dependent hypertension. It seems that 19, 20-EDP requires metabolic stabilization with a sEH inhibitor to be most effective in lowering BP, although both TPPU and 19, 20-EDP are so effective on their own that demonstrating additive or synergistic interactions is difficult.
AB - Mediators of antihypertensive actions of docosahexaenoic acid (DHA) are largely unknown. The omega-3 epoxide of DHA, 19, 20-EDP (epoxy docosapentaenoic acid), is metabolized by soluble epoxide hydrolase (sEH), which also metabolizes the anti-inflammatory and antihypertensive arachidonic acid epoxides, epoxyeicosatrienoic acids (EETs). Based in part on plasma levels of EDPs after a DHA-rich diet, we hypothesized that 19, 20-EDP contributes to the antihypertensive actions of DHA in angiotensin-II (Ang-II)-dependent hypertension. Treatment individually with 19, 20-EDP and a potent sEH inhibitor TPPU (1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea) significantly lowered blood pressure (BP) as compared with Ang-II-infused animals. The largest reduction in BP was obtained with the combination of 19, 20-EDP and TPPU, which was more efficacious than the combination of 14, 15-EET and TPPU. Oxylipin profiling revealed that 19, 20-EDP and 14, 15-EET infusion affected not only most metabolites of the P450 pathway but also renal levels of prostaglandin-E2. Our findings suggest that 19, 20-EDP is a mediator of the antihypertensive effects of DHA in Ang-II-dependent hypertension. It seems that 19, 20-EDP requires metabolic stabilization with a sEH inhibitor to be most effective in lowering BP, although both TPPU and 19, 20-EDP are so effective on their own that demonstrating additive or synergistic interactions is difficult.
KW - 19,20-epoxy docosapentaenoic acid
KW - angiotensin- II'dependent hypertension
KW - docosahexaenoic acid
KW - omega-3 polyunsaturated fatty acids
KW - soluble epoxide hydrolase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=84904266567&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904266567&partnerID=8YFLogxK
U2 - 10.1097/FJC.0000000000000094
DO - 10.1097/FJC.0000000000000094
M3 - Article
C2 - 24691274
AN - SCOPUS:84904266567
VL - 64
SP - 87
EP - 99
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
SN - 0160-2446
IS - 1
ER -