Endothelium‐dependent relaxations in sheep pulmonary arteries and veins: resistance to block by NG‐nitro‐L‐arginine in pulmonary hypertension
Endothelium‐dependent relaxations in sheep pulmonary arteries and veins: resistance to block by NG‐nitro‐L‐arginine in pulmonary hypertension
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绵羊肺动脉和静脉内皮依赖性松弛：肺动脉高压中 NG-硝基-L-精氨酸阻滞的抵抗
DOI：
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发表时间：
1995
影响因子：
7.3
通讯作者：
T. Cocks
中科院分区：
文献类型：
--
作者：
B. Kemp;J. Smolich;B. Ritchie;T. Cocks
研究了一氧化氮合酶抑制剂NG -硝基- L -精氨酸（L - NOARG）对内皮依赖性松弛到受体非依赖性药物离子霉素的作用，并在对照、短期和慢性肺动脉高压绵羊的分离肺动脉和静脉中进行了研究。所有血管节段在内皮素- 1作用下收缩至最佳活动力水平，以记录内皮依赖性松弛。肺动脉连续空气栓塞1天（短期）和14天（慢性）诱导肺动脉高压，分别与肺血管阻力增加2倍和3倍相关。3l‐NOARG （0.1 mM）使对照羊大中型肺动脉对离子霉素的最大松弛（Rmax）降低约70%。相比之下，L‐NOARG （0.1 mM）没有抑制短期和慢性肺动脉高压绵羊匹配血管中对离子霉素的Rmax。在慢性肺动脉高压动物中，离子霉素诱导的舒张对L‐NOARG抑制的抗性仅限于动脉血管，因为在大、中慢性肺动脉高压静脉中，离子霉素引起的舒张与对照静脉一样，被L‐NOARG消除。然而，短期肺动脉高压羊的大、中肺静脉对L - NOARG阻滞均有抵抗性。当细胞外K+浓度等压增加到30 mM时，大的短期肺动脉高压动脉对离子霉素的敏感性（pEC50）和Rmax都不受影响。硝苯地平（0.3 μm）一直存在，以防止高K+诱导的平滑肌收缩。然而，在这种高细胞外K+存在时，L‐NOARG （0.1 mM）完全抑制了对离子霉素的松弛，而在正常细胞外K+ (4.7 mM)中，L‐NOARG仅微弱抑制离子霉素的松弛。综上所述，绵羊空气栓塞后肺动脉高压的发生与内皮依赖性松弛对L - NOARG阻断的抵抗有关。L - NOARG抵抗的机制似乎是由于K+通道介导的备用血管扩张剂机制的上调，该机制可以补偿一氧化氮（NO）介导的松弛的损失。尽管这种机制在一氧化氮存在下保持功能“沉默”，但如果一氧化氮合成受损，它能够在肺动脉高压期间维持足够的内皮依赖性血管舒张。
1 The effect of the nitric oxide synthase inhibitor, NG‐nitro‐L‐arginine (L‐NOARG), on endothelium‐dependent relaxation to a receptor‐independent agent, ionomycin, was examined in isolated pulmonary arteries and veins from control, short‐term and chronic pulmonary hypertensive sheep. All vessel segments were contracted to optimal levels of active force with endothelin‐1 to record endothelium‐dependent relaxation. 2 Pulmonary hypertension was induced by continuous pulmonary artery air embolization for 1 day (short‐term) and 14 days (chronic) and was associated with a 2 and 3 fold increase in pulmonary vascular resistance respectively. 3 L‐NOARG (0.1 mM) reduced the maximum relaxation (Rmax) to ionomycin in large and medium‐sized pulmonary arteries from control sheep by approximately 70%. By contrast, L‐NOARG (0.1 mM) did not inhibit the Rmax to ionomycin in matched vessels from short‐term and chronic pulmonary hypertensive sheep. 4 Resistance of ionomycin‐induced relaxations to inhibition by L‐NOARG, was confined to the arterial vasculature in chronic pulmonary hypertensive animals, as relaxations to ionomycin in large and medium‐sized chronic pulmonary hypertensive veins were, like those in control veins, abolished by L‐NOARG. Both large and medium‐sized pulmonary veins from short‐term pulmonary hypertensive sheep, however, were resistant to block by L‐NOARG. 5 Neither sensitivity (pEC50) nor Rmax, to ionomycin in large, short‐term pulmonary hypertensive arteries was affected when the extracellular concentration of K+ was increased isotonically to 30 mM. Nifedipine (0.3 μm) was present throughout to prevent high K+‐induced smooth muscle contraction. In the presence of this high extracellular K+, however, L‐NOARG (0.1 mM) caused complete inhibition of the relaxation to ionomycin, whereas in normal extracellular K+ (4.7 mM), L‐NOARG only weakly inhibited ionomycin relaxations. 6 In conclusion, the onset of pulmonary hypertension in sheep following air embolization, is associated with the development of resistance of endothelium‐dependent relaxations to block by L‐NOARG. The mechanism of L‐NOARG resistance appears to be due to the up‐regulation of a K+ channel‐mediated backup vasodilator mechanism which can compensate for the loss of nitric oxide (NO)‐mediated relaxation. Although this mechanism remains functionally ‘silent’ in the presence of NO it is able to maintain adequate endothelium‐dependent vasodilatation during pulmonary hypertension if NO synthesis is compromised.
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影响因子：
3.3
作者：
X. Chen;C. Gillis
通讯作者：
X. Chen;C. Gillis
影响因子：
--
作者：
ASHMORE, RC;RODMAN, DM;STELZNER, TJ
通讯作者：
STELZNER, TJ
对绵羊进行连续空气栓塞会导致持续性肺动脉高压和肺血管反应性增加。
DOI：
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发表时间：
1988
期刊：
The American journal of pathology
影响因子：
--
作者：
Perkett,EA;Brigham,KL;Meyrick,B
通讯作者：
Meyrick,B
影响因子：
--
作者：
POST, JM;HUME, JR;WEIR, EK
通讯作者：
WEIR, EK
影响因子：
--
作者：
YUAN, XJ;GOLDMAN, WF;BLAUSTEIN, MP
通讯作者：
BLAUSTEIN, MP