INHIBITION OF ADENOSINE-INDUCED CORONARY VASODILATION BY BLOCK OF LARGE-CONDUCTANCE CA2+-ACTIVATED K+ CHANNELS
INHIBITION OF ADENOSINE-INDUCED CORONARY VASODILATION BY BLOCK OF LARGE-CONDUCTANCE CA2+-ACTIVATED K+ CHANNELS
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DOI：
10.1152/ajpheart.1994.267.4.h1455
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发表时间：
1994-10-01
影响因子：
4.8
通讯作者：
PRICE, JM
中科院分区：
文献类型：
--
作者：
CABELL, F;WEISS, DS;PRICE, JM
本研究的目的是探讨大电导钙激活钾（大电导K-Ca）通道对腺苷（Ado）和硝普钠介导的小冠状动脉舒张的贡献。将犬心外膜下动脉（120 mmHg时为170 +/- 23 μ m）作为体外加压血管进行研究。压力-直径实验显示在生理压力范围内的肌源性张力。血栓素A（2）类似物9，11-双脱氧-11 α，9 α-环氧-甲氧前列腺素F-2 α（U-46619）可增加张力。四乙基铵（TEA（+）; 1 mM）在0.1 - 10 μ M的Ado浓度范围内显著抑制cAMP诱导的[并暗示腺苷3 '，5'-环一磷酸（cAMP）诱导的]舒张，在1 μ M Ado时抑制最大（61 +/- 8%）。大电导K-Ca-通道阻断剂iberotoxin（IbTX; 0.01-0.1 μ M）以浓度依赖性方式抑制K-Ca-通道的舒张。IbTX的抑制随着血管压力的增加而增加（即，40 mmHg时45 +/- 12%，120 mmHg时83 +/- 20%）。TEA（+）对硝普钠诱导的舒张作用最小（8 +/- 3%）。乙酰胆碱和缓激肽也有类似的结果。这些结果表明，（在直径< 200 μ m的狗冠状动脉中）大电导K-Ca通道调节可能在cAMP介导的舒张中起主要作用，但在鸟苷3 '，5'-环一磷酸介导的舒张中不显著。
The aim of the present study was to investigate the contribution of large-conductance calcium-activated potassium (large-conductance K-Ca) channels to adenosine (Ado)- and nitroprusside-mediated relaxation in small coronary arteries. Canine subepicardial arteries (170 +/- 23 mu m at 120 mmHg) were studied as in vitro pressurized vessels. Pressure-diameter experiments showed myogenic tone over a physiological range of pressures. Tone was increased with the thromboxane A(2) analogue 9,11-dideoxy-11 alpha,9 alpha-epoxy-methanoprostaglandin F-2 alpha (U-46619). Tetraethylammonium (TEA(+); 1 mM) significantly inhibited Ado-induced [and by implication, adenosine 3',5'-cyclic monophosphate (cAMP)-induced] relaxations at Ado concentrations ranging from 0.1 to 10 mu M with maximal inhibition (61 +/- 8%) at 1 mu M Ado. The large-conductance K-Ca-channel blocker iberiotoxin (IbTX; 0.01-0.1 mu M) inhibited Ado-mediated relaxation in a concentration-dependent manner. Inhibition by IbTX increased with increasing vessel pressure (i.e., 45 +/- 12% at 40 mmHg and 83 +/- 20% at 120 mmHg). TEA(+) had a minimal effect (8 +/- 3%) on relaxation induced by nitroprusside. Similar results were found with acetylcholine and bradykinin. These results suggest that (in dog coronary arteries with diameter < 200 mu m) large-conductance K-Ca-channel modulation may play a major role in cAMP-mediated relaxation but is not significant in guanosine 3',5'-cyclic monophosphate-mediated relaxation.