Salt modulates vascular response through adenosine A(2A) receptor in eNOS-null mice: role of CYP450 epoxygenase and soluble epoxide hydrolase.
Salt modulates vascular response through adenosine A(2A) receptor in eNOS-null mice: role of CYP450 epoxygenase and soluble epoxide hydrolase.
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DOI：
10.1007/s11010-010-0686-0
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发表时间：
2011-04
影响因子：
4.3
通讯作者：
Falck, John R.
中科院分区：
文献类型：
--
作者：
Nayeem, Mohammed A.;Zeldin, Darryl C.;Boegehold, Matthew A.;Falck, John R.
高盐（HS）摄入可改变小鼠动脉张力，一氧化氮（NO）可介导某些受体介导的血管反应。本研究的主要目的是探讨腺苷诱导的内皮型一氧化氮合酶（eNOS）+/+和eNOS-/-小鼠血管反应的机制。（eNOS+/+和eNOS−/−）通过乙酰胆碱（ACh）喂食4%（HS）或0.45%（NS）NaCl饮食，NECA（腺苷类似物）、CGS 21680（A2 A AR激动剂）、MS-PPOH（β-环氧合酶阻断剂; 10−5 M）、AUDA（sEH阻断剂; 10−5 M）和DDMS（CYP 4A阻断剂; 10−5 M）。HS-eNOS+/+组ACh反应性（+59.3 ± 6.3%）高于NS-eNOS+/+组（+33.3 ± 8.0%; P < 0.05）。然而，HS-eNOS-/-和NS-eNOS-/-均无反应。HS-eNOS−/−（+37.4 ± 3.2%）的NECA反应高于NS-eNOS−/−（+7.4.0 ± 3.8%; P < 0.05）。CGS 21680-反应在HS-eNOS−/−（+45.4 ± 5.2%）中也高于NS-eNOS−/−（+5.1 ± 5.0%; P < 0.05）。在HS-eNOS−/−中，CGS 21680反应被MS-PPOH降低（+7.3 ± 3.2%; P < 0.05）。在NS-eNOS−/−中，AUDA（+38.2 ± 3.3%; P < 0.05）和DDMS（+30.1 ± 4.1%; P < 0.05）增加了CGS 21680反应。与NS相比，HS增加了eNOS+/+（35%; P < 0.05）和eNOS−/−（61%; P < 0.05）的CYP 2 J2，但降低了eNOS+/+（74%; P < 0.05）和eNOS−/−（40%; P < 0.05）的sEH。同样，CYP 4A在HS-eNOS+/+（35%; P < 0.05）和HS-eNOS−/−（34%; P < 0.05）中降低。这些数据表明，NS通过sEH和CYP 4A引起eNOS+/+和eNOS−/−的血管舒张减少。然而，HS通过eNOS+/+和eNOS-/-中的β-环氧合酶触发可能的A2 AAR诱导的舒张。
High salt (HS) intake can change the arterial tone in mice, and the nitric oxide (NO) acts as a mediator to some of the receptors mediated vascular response. The main aim of this study was to explore the mechanism behind adenosine-induced vascular response in HS-fed eNOS+/+ and eNOS−/− mice The modulation of vascular response by HS was examined using aortas from mice (eNOS+/+ and eNOS−/−) fed 4% (HS) or 0.45% (NS) NaCl-diet through acetylcholine (ACh), NECA (adenosine-analog), CGS 21680 (A2A AR-agonist), MS-PPOH (CYP epoxygenase-blocker; 10−5 M), AUDA (sEH-blocker; 10−5 M), and DDMS (CYP4A-blocker; 10−5 M). ACh-response was greater in HS-eNOS+/+ (+59.3 ± 6.3%) versus NS-eNOS+/+ (+33.3 ± 8.0%; P < 0.05). However, there was no response in both HS-eNOS−/− and NS-eNOS−/−. NECA-response was greater in HS-eNOS−/− (+37.4 ± 3.2%) versus NS-eNOS−/− (+7.4.0 ± 3.8%; P < 0.05). CGS 21680-response was also greater in HS-eNOS−/− (+45.4 ± 5.2%) versus NS-eNOS−/−(+5.1 ± 5.0%; P < 0.05). In HS-eNOS−/−, the CGS 21680-response was reduced by MS-PPOH (+7.3 ± 3.2%; P < 0.05). In NS-eNOS−/−, the CGS 21680-response was increased by AUDA (+38.2 ± 3.3%; P < 0.05) and DDMS (+30.1 ± 4.1%; P < 0.05). Compared to NS, HS increased CYP2J2 in eNOS+/+ (35%; P < 0.05) and eNOS−/− (61%; P < 0.05), but decreased sEH in eNOS+/+ (74%; P < 0.05) and eNOS−/− (40%; P < 0.05). Similarly, CYP4A decreased in HS-eNOS+/+ (35%; P < 0.05) and HS-eNOS−/− (34%; P < 0.05). These data suggest that NS causes reduced-vasodilation in both eNOS+/+ and eNOS−/− via sEH and CYP4A. However, HS triggers possible A2AAR-induced relaxation through CYP epoxygenase in both eNOS+/+ and eNOS−/−.
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影响因子：
2.9
作者：
Faraci, FM;Sobey, CG
通讯作者：
Sobey, CG
影响因子：
20.1
作者：
Li, PL;Chen, CL;Campbell, WB
通讯作者：
Campbell, WB
影响因子：
20.1
作者：
Campbell, WB;Gebremedhin, D;Harder, DR
通讯作者：
Harder, DR
影响因子：
3.3
作者：
HIRAI, T;VISNESKI, MD;MUSCH, TI
通讯作者：
MUSCH, TI
DOI：
10.1073/pnas.97.17.9747
发表时间：
2000-08-15
影响因子：
11.1
作者：
Brandes, RP;Schmitz-Winnenthal, FH;Busse, R
通讯作者：
Busse, R