经G—蛋白敏感的跨膜信号通路调控心血管肌源性张力

本研究探讨低氧和ＡｌＦ－４等药物经Ｇ－蛋白敏感的跨膜信号通路对心血管肌源性张力的调控作用。在含有稳定表达Ｎａ＋－Ｃａ２＋交换蛋白的ＣＫ１．４细胞中，用ｆｕｒａ－２荧光影像确定细胞低氧对胞浆游离Ｃａ２＋［Ｃａ２＋］ｉ的影响。在离体犬心乳头肌、颈动脉、主动脉及肺动脉恒温灌流样本中，用张力－电换能器测量低氧灌流和ＡｌＦ－４等药物对心血管肌源性张力的影响。在整体犬体内，按拉丁方设计，用１２５Ｉｓｏｄ－１获得不同剂量ＶＩＳＡ高效剂细胞内分布等药代动力学参数。结果表明：①在ＣＫ１．４细胞中，低氧抑制Ｎａ＋－Ｃａ２＋交换蛋白，产生Ｃａ２＋内流，升高［Ｃａ２＋］ｉ；②低氧灌流削弱ＡｌＦ－４所致的血管收缩而明显易化Ｃａ２＋内流所致的心乳头肌收缩，与结果１）吻合；③ＶＩＳＡ高效剂分布至细胞内，协同ＡｌＦ－４，模拟并激活Ｇ－蛋白敏感的跨膜信号通路，显著改善低氧所致的Ｎａ＋－Ｃａ２＋交换蛋白等跨膜大分子和心血管收缩蛋白氧化损害。

REGULATION OF CARDIOVASCULAR MYOGENIC TONE VIA G PROTEIN SENSITIVE TRANSMEMBRANE SIGNAL PATHWAYS

Effects of cellular hypoxia on [Ca2+]i in CK1.4 cells expressed Na(+)-Ca2+ exchange protein were determined by fura-2 fluorescence imaging. In vitro perfused of canine cardiovascular samples (37 degrees C), changes of aortic, cervical, pulmonary arterial smooth myogenic tone and cardiac papillary myogenic tone were measured by mechanic-electrical transducers via a computer-aid autosampling system. In the whole dogs, pharmacolkinetic parameters of a VISA agent at three dosages were calculated by 125Isod-1 scintillation counting according to a 6 x 6 statistical model. The results indicated that 1. hypoxia inhibited the Na(+)-Ca2+ exchange protein induced by and elevated Ca(2+)-influx and [Ca2+]i in the CK1.4 cells; 2. hypoxic perfusions depressed the AlF4-(-)activated myogenic vasoconstriction in aortic, cervical and pulmonary arteries, but facilitated the cardiac papillary myogenic contraction Ca(2+)-influx-induced, the finding was consistent with the first result; and 3. the VISA agent distributed in the cell together with AlF4- simulated and activated G-protein-sensitive transmembrane sygnal, and signhificantly improved the oxidative injuries of the transmembrane macrowolecules and cardiovascular contraction proteins such as Na(+)-Ca2+ exchange protein induced by hypoxia.