Karabacak K, Kaya E, Ulusoy K G, Seyrek M, Kurtoglu M, Doganci S, Yildirim V, Yildiz O, Demirkilic U
Department of Cardiovascular Surgery, Gulhane Faculty of Medicine, Ankara, Turkey.
Eur Rev Med Pharmacol Sci. 2015 Apr;19(8):1498-504.
Taurine is an abundant amino acid that is widely distributed in human and animal tissues. Pharmacodynamic studies show that taurine has hypotensive and myocardial protective effects. Studies in isolated tissue baths show that taurine relaxes precontracted arteries. This study aimed to show the effects of taurine on human internal mammary artery (IMA) in vitro and to explain the mechanisms of its effects.
The response in the IMA was recorded isometrically by a force displacement transducer in isolated organ baths. Taurine (20, 40, 80 mM) was added to organ baths after precontraction with KCl (45 mM) or serotonin (5-HT, 30 µM). Taurine-induced relaxations were also tested in the presence of the cyclooxygenase inhibitor indomethacin (10 µM), the nitric oxide synthase inhibitor L-NAME (100 µM), the large conductance Ca2+-activated K+ channel inhibitor tetraethylammonium (TEA, 1 mM), the ATP-sensitive K+ channel inhibitor glibenclamide (GLI, 10 µM), the voltage-sensitive K+ channel inhibitor 4-aminopyridine (4-AP, 1 mM) and the inward rectifier K+ channel inhibitor barium chloride (BaCl2, 30 µM).
Taurine did not affect the resting tone of IMA. However, it produced relaxation in the 5-HT and KCl -precontracted preparations. The relaxation to IMA was not affected by GLI, 4-AP, BaCl2, indomethacin and L-NAME. But, TEA inhibited taurine -induced relaxations significantly (p < 0.05).
The preincubation of IMA with taurine antagonized KCl and 5-HT induced contractions in a concentration dependent manner, while it did not affect the resting tone. The relaxations to taurine were significantly antagonized by pretreatment with TEA. These results suggest that mechanism of vasodilator effect of taurine in IMA may be the activation of large conductance Ca2+-activated K+ channels.
牛磺酸是一种含量丰富的氨基酸,广泛分布于人和动物组织中。药效学研究表明,牛磺酸具有降压和心肌保护作用。在离体组织浴实验中显示,牛磺酸可使预收缩的动脉舒张。本研究旨在揭示牛磺酸对人乳内动脉(IMA)的体外作用,并解释其作用机制。
在离体器官浴中,通过力位移换能器等长记录IMA的反应。在用氯化钾(45 mM)或5-羟色胺(5-HT,30 μM)预收缩后,将牛磺酸(20、40、80 mM)加入器官浴中。还在存在环氧化酶抑制剂吲哚美辛(10 μM)、一氧化氮合酶抑制剂L- NAME(100 μM)、大电导钙激活钾通道抑制剂四乙铵(TEA,1 mM)、ATP敏感性钾通道抑制剂格列本脲(GLI,10 μM)、电压敏感性钾通道抑制剂4-氨基吡啶(4-AP,1 mM)和内向整流钾通道抑制剂氯化钡(BaCl2,30 μM)的情况下,测试牛磺酸诱导的舒张作用。
牛磺酸不影响IMA的静息张力。然而,它可使5-HT和氯化钾预收缩的制剂舒张。对IMA的舒张作用不受GLI、4-AP、BaCl2、吲哚美辛和L- NAME的影响。但是,TEA显著抑制牛磺酸诱导的舒张作用(p < 0.05)。
IMA与牛磺酸预孵育以浓度依赖的方式拮抗氯化钾和5-HT诱导的收缩,而不影响静息张力。用TEA预处理可显著拮抗对牛磺酸的舒张反应。这些结果表明,牛磺酸在IMA中的血管舒张作用机制可能是激活大电导钙激活钾通道。