期刊
JOURNAL OF PHARMACOLOGICAL SCIENCES
卷 141, 期 1, 页码 64-69出版社
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2019.09.006
关键词
Up(4)A; Coronary microcirculation; Relaxation; Smooth muscle cells; Adenosine
资金
- Southwest Medical University China [MEPSCKL201301]
- Karolinska Institutet
- Loo and Hans Ostermans Stiftelse [201801213]
- Sigurt and Elsa Goljes Memorial Foundation
- Lars Hiertas Minne Foundation [FO2018-0156]
- [NIH-HL027339]
Activation of both adenosine A(2A) and A(2B) receptors (A(2B)R) contributes to coronary vasodilation. We previously demonstrated that uridine adenosine tetraphosphate (Up(4)A) is a novel vasodilator in the porcine coronary microcirculation, acting mainly on A(2A)R in smooth muscle cells (SMC). We further investigated whether activation of A(2B)R is involved in Up(4)A-mediated coronary SMC relaxation. Both A(2A)R and A(2B)R may stimulate H2O2 production leading to activation of K(ATP )channels in SMCs, we also studied the involvement of H2O2 and K-ATP channels in Up(4)A-mediated effect. Coronary small arteries dissected from the apex of porcine hearts were mounted on wire myograph for Up(4)A concentration responses. Up(4)A-induced coronary SMC relaxation was attenuated by A(2A)R but not A(2B)R antagonism or non-selective P2R antagonism, despite greater endogenous A(2B)R expression vs. A(2A)R in both coronary small arteries and primary cultured coronary SMCs. Moreover, Up(4)A-induced coronary SMC relaxation was blunted by H2O2 catabolism. This effect was not altered by K-ATP channel blockade. Combination of H2O2 catabolism and A(2A)R antagonism attenuated Up4A-induced coronary SMC relaxation to the similar extent as A(2A)R antagonism alone. Collectively, Up(4)A-induced porcine coronary SMC relaxation is mediated by activation of A(2A)R-H2O2 pathway. This process does not involve A(2B)R, P2R or K-ATP channels. (C) 2019 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据