| Title | Effect of PGE2 on DA tone by EP4 modulating Kv channels with different oxygen tension between preterm and term |
| Authors | Fan, Fenling Ma, Aiqun Guan, Youfei Huo, Jianhua Hu, Zhi Tian, Hongyan Chen, Lihong Zhu, Sen Fan, Lihong |
| Affiliation | Xi An Jiao Tong Univ, Affiliated Hosp 1, Cardiovasc Dept, Xian 710061, Peoples R China. Natl Minist Educ, Key Lab Environm & Gene Related Dis, Res Lab Ion Channelopathy, Xian 710061, Peoples R China. Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China. Xi An Jiao Tong Univ, Ctr Cardiovasc Med, 277 W Yanta Rd, Xian 710061, Peoples R China. |
| Keywords | PDA PGE2 receptor 4 Whole-Cell Patch-Clamp Kv channel Medicine RABBIT DUCTUS-ARTERIOSUS GATED POTASSIUM CHANNELS SMOOTH-MUSCLE-CELLS PROSTANOID RECEPTORS O-2 CONSTRICTION PGE(2) RECEPTORS FETAL EXPRESSION BIRTH RAT |
| Issue Date | 2011 |
| Publisher | international journal of cardiology |
| Citation | INTERNATIONAL JOURNAL OF CARDIOLOGY.2011,147,(1),58-65. |
| Abstract | Objective: To investigate common downstream mechanism of PGE2 and O2-sensitive voltage-dependent potassium (Kv) channels in preterm and term DA tone regulations, for suggesting respective prescriptions for preterm and term PDA. Study design: The expressions of Kv1.2, 1.5 and 2.1 were compared between preterm and term in rabbit and human DAs at mRNA and protein levels; DA contracting responses caused by O2, Kv channels blocker 4-AP, EP4 antagonist GW627368X, and PGE2 reduce using vessels rings and Whole-Cell Patch-Clamp were explored. Results: Kv 1.2 and 2.1 expressions were developed with pregnant age in preterm DA and decreased after birth with oxygen stimulation in term DA. GW627368X led significant DA constriction and DASMC IK current decrease in preterm, which was slimier to 4-AP effects, but just slightly influenced on DA tension and DASMC IK current at term. In addition, PGE2 led great DA dilation and IK current increase of DASMC in preterm but not in term. These DA tension and IK current changes were in line with Kv channel expressions. Conclusion: Higher levels of PGE2 binds with GPCR EP4, which activates G-protein to couple with O2-sensitive Kv channels and to open them, leading to DA vasorelaxation in the fetus. It indicates that EP4 inhibitors, instead of PGE2 or its analogue PGE1, may be a selectable strategy for preterm PDA. (C) 2009 Elsevier Ireland Ltd. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/241412 |
| ISSN | 0167-5273 |
| DOI | 10.1016/j.ijcard.2009.07.045 |
| Indexed | SCI(E) |
| Appears in Collections: | 医学部待认领 |
