NG-单甲基-L-精氨酸而非格列本脲抑制缺氧诱导的兔离体冠状动脉舒张。

Inhibition of hypoxia-induced relaxation of rabbit isolated coronary arteries by NG-monomethyl-L-arginine but not glibenclamide.

作者信息

Jiang C, Collins P

机构信息

Department of Cardiac Medicine, University of London.

出版信息

Br J Pharmacol. 1994 Mar;111(3):711-6. doi: 10.1111/j.1476-5381.1994.tb14795.x.

DOI:10.1111/j.1476-5381.1994.tb14795.x

PMID:8019749

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1910108/

Abstract

The effects of NG-monomethyl-L-arginine, tetrodotoxin and glibenclamide on hypoxia-induced coronary artery relaxation, induced by bubbling Krebs solution with 95% N2 and 5% CO2 instead of 95% O2 and 5% CO2, were assessed by measuring the changes in isometric tension in isolated epicardial coronary artery rings of the rabbit. In addition, the effects of glibenclamide on the relaxation induced by adenosine were investigated. 2. Hypoxia caused a transient relaxation of 38 +/- 3% (P < 0.01) and 17 +/- 2% (P < 0.01) in endothelium-intact or -denuded arteries respectively. NG-monomethyl-L-arginine (30 and 100 microM) inhibited the relaxation in endothelium-intact rings to 31 +/- 2% (P < 0.05) and 16 +/- 2% (P < 0.01) respectively and slightly but significantly attenuated the relaxation in endothelium-denuded rings to 15 +/- 1% and 13 +/- 1% (P < 0.05) respectively. 3. Glibenclamide, a potassium channel inhibitor, did not significantly after the hypoxia-induced relaxation. 4. Incubation with tetrodotoxin (3 and 10 microM) for 30 min reduced the relaxation to 31 +/- 3% (P < 0.05) and 14 +/- 2% (P < 0.01), and 14 +/- 2% (P < 0.05) and 11 +/- 1% (P < 0.05) in endothelium-intact and -denuded rings respectively. However, indomethacin (10 microM), atropine (1 microM), propranolol (10 microM) and phentolamine (10 microM) did not significantly affect the relaxation. 5. Adenosine (1, 10 and 100 MicroM) caused relaxation of 6 +/- 1%, 52 +/-3% and 97 +/-2% respectively in endothelium-denuded rings precontracted with prostaglandin F2alpha (PGF2 alpha, 3 MicroM) and the relaxation was markedly inhibited by 8-phenyltheophylline. Furthermore, glibenclamide (1 and 10 MicroM) reduced the relaxation induced by adenosine (1, 10 and 100 MicroM) to 2 +/-1% (P<0.05), 38 =/-3% (P<0.05) and 85 +/-2%(P<0.05), and 0.6 +/- 0.4% (P<0.05), 27 +/- 4% (P<0.05) and 72 +/- 4% (P<0.01) respectively, in these endothelium-denuded preparations.6. These data suggest that hypoxia-induced relaxation is mediated by the release of nitric oxide rather than by the activation of glibenclamide-sensitive potassium channels in rabbit isolated coronary arteries. A neurogenic mechanism partially modulates the relaxation, possibly by activating non-adrenergic and noncholinergic nerve endings. The inhibition by glibenclamide on adenosine-induced relaxation in isolated coronary arteries may help to explain the fact that glibenclamide inhibits hypoxic coronary relaxation in perfused hearts but not in isolated coronary preparations.

摘要

通过测量兔离体心外膜冠状动脉环等长张力的变化，评估了NG-单甲基-L-精氨酸、河豚毒素和格列本脲对用95%N₂和5%CO₂而非95%O₂和5%CO₂鼓泡的Krebs溶液诱导的缺氧性冠状动脉舒张的影响。此外，还研究了格列本脲对腺苷诱导的舒张的影响。2. 缺氧分别使完整内皮或去内皮动脉产生38±3%（P<0.01）和17±2%（P<0.01）的短暂舒张。NG-单甲基-L-精氨酸（30和100μM）分别将完整内皮环中的舒张抑制至31±2%（P<0.05）和16±2%（P<0.01），并轻微但显著地将去内皮环中的舒张减弱至15±1%和13±1%（P<0.05）。3. 钾通道抑制剂格列本脲对缺氧诱导的舒张无显著影响。4. 用河豚毒素（3和10μM）孵育30分钟后，完整内皮环和去内皮环中的舒张分别降至31±3%（P<0.05）和14±2%（P<0.01），以及14±2%（P<0.05）和11±1%（P<0.05）。然而，吲哚美辛（10μM）、阿托品（1μM）、普萘洛尔（10μM）和酚妥拉明（10μM）对舒张无显著影响。5. 腺苷（1、10和100μM）分别使预先用前列腺素F2α（PGF2α，3μM）预收缩的去内皮环产生6±1%、52±3%和97±2%的舒张，且该舒张被8-苯基茶碱显著抑制。此外，格列本脲（1和10μM）分别将腺苷（1、10和100μM）诱导的舒张在这些去内皮制剂中降至2±1%（P<0.05）、38±3%（P<0.05）和85±2%（P<0.05），以及0.6±0.4%（P<0.05）、27±4%（P<0.05）和72±4%（P<0.01）。6. 这些数据表明，在兔离体冠状动脉中，缺氧诱导的舒张是由一氧化氮释放介导的，而非由格列本脲敏感的钾通道激活介导。一种神经源性机制部分调节该舒张，可能是通过激活非肾上腺素能和非胆碱能神经末梢。格列本脲对离体冠状动脉中腺苷诱导的舒张的抑制作用可能有助于解释格列本脲抑制灌注心脏中的缺氧性冠状动脉舒张但不抑制离体冠状动脉制剂中的缺氧性冠状动脉舒张这一事实。