Activity of Endothelium-Derived Hyperpolarizing Factor Is Augmented in Monocrotaline-Induced Pulmonary Hypertension of Rat Lungs
Activity of Endothelium-Derived Hyperpolarizing Factor Is Augmented in Monocrotaline-Induced Pulmonary Hypertension of Rat Lungs
复制标题
野百合碱诱导的大鼠肺肺动脉高压中内皮衍生的超极化因子的活性增强
DOI：
10.1159/000101778
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发表时间：
2007
影响因子：
1.7
通讯作者：
Y. Fukuchi
中科院分区：
文献类型：
--
作者：
Y. Morio;N. Homma;Hideki Takahashi;Akihito Yamamoto;T. Nagaoka;Koichi Sato;M. Muramatsu;Y. Fukuchi
内皮依赖性血管舒张信号的机制涉及一氧化氮、前列环素和内皮源性超极化因子（EDHF）三种成分。虽然EDHF与一氧化氮和前列环素不同，但它需要激活Ca 2+敏感性K+通道（KCa）和细胞色素P450代谢产物。然而，EDHF在肺循环中的生理作用尚不清楚。因此，我们测试了EDHF是否会调节对照组和野百合碱（MCT）诱导的肺动脉高压大鼠肺中的血管张力。联合使用KCa阻断剂、卡律巴毒素（50 nM）和蜂毒肽（50 nM）抑制EDHF，可增加MCT诱导的高血压肺的基线血管张力。Thapsigargin（TG; 100 nM）是一种Ca-ATP酶抑制剂，在MCT诱导的高血压肺中引起更大的EDHF介导的血管舒张。TG诱导的血管舒张被Charybdotoxin-apamin组合消除。磺胺苯吡唑（10 µM）是一种细胞色素P450抑制剂，可减少MCT诱导的高血压肺中TG诱导的血管舒张。RT-PCR分析显示MCT处理的肺中KCa mRNA增加。这些结果表明，通过细胞色素P450代谢物的改变和MCT诱导的肺动脉高压中KCa表达的上调，至少部分增强了紧张性EDHF活性。
The mechanism of endothelium-dependent vasodilator signaling involves three components such as nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). Although EDHF is distinct from nitric oxide and prostacyclin, it requires activation of Ca2+-sensitive K+ channels (KCa) and cytochrome P450 metabolites. However, the physiological role of EDHF in the pulmonary circulation is unclear. Thus, we tested if EDHF would regulate vascular tone in rat lungs of control and monocrotaline (MCT)-induced pulmonary hypertension. Inhibition of EDHF with a combination of KCa blockers, charybdotoxin (50 nM) plus apamin (50 nM), increased baseline vascular tone in MCT-induced hypertensive lungs. Thapsigargin (TG; 100 nM), an inhibitor of Ca-ATPase, caused greater EDHF-mediated vasodilation in MCT-induced hypertensive lungs. TG-induced vasodilation was abolished with the charybdotoxin-apamin combination. Sulfaphenazole (10 µM), a cytochrome P450 inhibitor, reduced the TG-induced vasodilation in MCT-induced hypertensive lungs. RT-PCR analysis exhibited an increase in KCa mRNA in MCT-treated lungs. These results indicate the augmentation of tonic EDHF activity, at least in part, through the alteration in cytochrome P450 metabolites and the upregulation of KCa expression in MCT-induced pulmonary hypertension.
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DOI：
10.1152/ajpheart.00376.2003
发表时间：
2003-10-01
影响因子：
4.8
作者：
Marrelli, SP;Eckmann, MS;Hunte, MS
通讯作者：
Hunte, MS
DOI：
10.1152/ajplung.2000.279.5.l857
发表时间：
2000-11-01
影响因子：
4.9
作者：
Cornfield, DN;Resnik, ER;Abman, SH
通讯作者：
Abman, SH
P-450 代谢物可改变缺氧性肺血管收缩作用。
DOI：
10.1152/ajpheart.2000.279.4.h1526
发表时间：
2000
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
--
作者：
Zhu,D;Birks,EK;Dawson,CA;Patel,M;Falck,JR;Presberg,K;Roman,RJ;Jacobs,ER
通讯作者：
Jacobs,ER
DOI：
10.1152/ajpheart.1997.272.2.h806
发表时间：
1997-02-01
影响因子：
4.8
作者：
Resta, TC;Gonzales, RJ;Walker, BR
通讯作者：
Walker, BR
影响因子：
15.9
作者：
DECATERINA, R;LIBBY, P;LIAO, JK
通讯作者：
LIAO, JK