| First Author | Yadav VR | Year | 2016 |
| Journal | Mol Cell Biochem | Volume | 422 |
| Issue | 1-2 | Pages | 197-206 |
| PubMed ID | 27629787 | Mgi Jnum | J:302882 |
| Mgi Id | MGI:6510899 | Doi | 10.1007/s11010-016-2821-z |
| Citation | Yadav VR, et al. (2016) Vascular endothelial over-expression of soluble epoxide hydrolase (Tie2-sEH) enhances adenosine A1 receptor-dependent contraction in mouse mesenteric arteries: role of ATP-sensitive K(+) channels. Mol Cell Biochem 422(1-2):197-206 |
| abstractText | Soluble epoxide hydrolase (sEH) converts epoxyeicosatrienoic acids that are endothelium-derived hyperpolarizing factors into less active dihydroxyeicosatrienoic acids. Previously, we reported a decrease in adenosine A1 receptor (A1AR) protein levels in sEH knockout (sEH(-/-)) and an increase in sEH and A1AR protein levels in A2AAR(-/-) mice. Additionally, KATP channels are involved in adenosine receptor (AR)-dependent vascular relaxation. Thus, we hypothesize that a potential relationship may exist among sEH over-expression, A1AR upregulation, inactivation of KATP channels, and increased in vascular tone. We performed DMT myograph muscle tension measurements and western blot analysis in isolated mouse mesenteric arteries (MAs) from wild-type (WT) and endothelial over-expression of sEH (Tie2-sEH Tr) mice. Our data revealed that NECA (a non-selective adenosine receptors agonist)-induced relaxation was significantly reduced in Tie2-sEH Tr mice, and CCPA (A1AR agonist)-induced contraction was increased in Tie2-sEH Tr mice. A1AR-dependent contraction in Tie2-sEH Tr mice was significantly attenuated by pharmacological inhibition of CYP4A (HET0016, 10 microM), PKCalpha (GO6976, 1 microM), and ERK1/2 (PD58059, 1 microM). Our western blot analysis revealed significantly higher basal protein expression of CYP4A, A1AR, and reduced p-ERK in MAs of Tie2-sEH Tr mice. Notably, pinacidil (KATP channel opener)-induced relaxation was also significantly reduced in MAs of Tie2-sEH Tr mice. Furthermore, KATP channel-dependent relaxation in MAs was enhanced by inhibition of PKCalpha and ERK1/2 in WT but not Tie2-sEH Tr mice. In conclusion, our data suggest that over-expression of sEH enhances A1AR-dependent contraction and reduces KATP channel-dependent relaxation in MAs. These results suggest a possible interaction between sEH, A1AR, and KATP channels in regulating vascular tone. |
