Liu M H, Floten H S, Furnary A P, Yim A P, He G W
Cardiovascular Research, Starr Academic Center for Cardiac Surgery, Providence Heart Institute, St Vincent Hospital, Portland, Oregon, USA.
Ann Thorac Surg. 2001 Feb;71(2):636-41. doi: 10.1016/s0003-4975(00)02249-9.
Arterial grafts for coronary artery bypass grafting such as the internal mammary artery (IMA) may develop spasm perioperatively. The purpose of this study was to investigate the effects of the potassium channel opener, aprikalim, on the receptor-mediated vasoconstriction in the human IMA in vitro.
We studied 160 IMA rings taken from coronary artery surgery in organ baths. The interaction between aprikalim and four vasoconstrictors 5-hydroxytryptamine (5-HT), norepinephrine (NE), endothelin-1 (ET-1), and angiotensin II (AII) was investigated in two ways.
Aprikalim relaxed IMA rings precontracted by the vasoconstrictors to 66.40 +/- 5.9% for 5-HT (EC50: -6.78 +/- 0.26 LogM), 57.40 +/- 5.5% for NE (-6.54 +/- 0.39 LogM), 81.00 +/- 6.7% for ET-1 (-6.58 +/- 0.26 LogM), and 93.90 +/- 2.5% for AII (-7.80 +/- 0.23 LogM). The relaxation in endothelium-denuded rings contracted by AII was similar to that in the endothelium-intact rings. The relaxation was attenuated by glibenclamide (3 microM) in 5-HT or NE-precontracted IMA. Pretreatment with aprikalim at 1 microM depressed AII-induced contraction (33.20 +/- 7.5% versus 59.70 +/- 7.3%, p < 0.01) but only shifted the curves rightward for 5-HT or NE (EC50 3.1 or 4.3-folds higher, p < 0.05), whereas at 30 microM it also significantly depressed the maximal contraction for 5-HT (35.70 +/- 4.9% versus 103.30 +/- 9.8%, p < 0.001) and NE (90.60 +/- 15.6% versus 125.60 +/- 7.9%, p < 0.05). In contrast, aprikalim did not significantly depress the contraction induced by ET-1 (p > 0.05).
We conclude that aprikalim has vasorelaxant effects on IMA and the effect is vasoconstrictor-selective and endothelium-independent. Aprikalim may provide clinically useful vasorelaxant effects in coronary bypass surgery.
用于冠状动脉旁路移植术的动脉移植物，如乳内动脉（IMA），在围手术期可能会发生痉挛。本研究的目的是在体外研究钾通道开放剂阿普卡林对人IMA中受体介导的血管收缩的影响。
我们在器官浴中研究了取自冠状动脉手术的160个IMA环。通过两种方式研究了阿普卡林与四种血管收缩剂5-羟色胺（5-HT）、去甲肾上腺素（NE）、内皮素-1（ET-1）和血管紧张素II（AII）之间的相互作用。
阿普卡林使由血管收缩剂预收缩的IMA环松弛，对于5-HT，松弛至66.40±5.9%（半数有效浓度：-6.78±0.26 LogM）；对于NE，松弛至57.40±5.5%（-6.54±0.39 LogM）；对于ET-1，松弛至81.00±6.7%（-6.58±0.26 LogM）；对于AII，松弛至93.90±2.5%（-7.80±0.23 LogM）。由AII收缩的内皮剥脱环的松弛与内皮完整环的松弛相似。在5-HT或NE预收缩的IMA中，格列本脲（3 microM）减弱了阿普卡林的松弛作用。用1 microM阿普卡林预处理可抑制AII诱导的收缩（33.20±7.5%对59.70±7.3%，p<0.01），但仅使5-HT或NE的曲线右移（半数有效浓度高3.1或4.3倍，p<0.05），而在30 microM时，它也显著抑制5-HT（35.70±4.9%对103.30±9.8%，p<0.001）和NE（90.6±15.6%对125.60±7.9%，p<0.05）的最大收缩。相比之下，阿普卡林对ET-1诱导的收缩没有显著抑制作用（p>0.05）。
我们得出结论，阿普卡林对IMA具有血管舒张作用，且该作用具有血管收缩剂选择性和内皮非依赖性。阿普卡林可能在冠状动脉旁路手术中提供临床上有用的血管舒张作用。
