Siegel G, Schnalke F, Rückborn K, Müller J, Hetzer R
Institute of Physiology, Free University of Berlin, Germany.
Agents Actions Suppl. 1992;37:320-32. doi: 10.1007/978-3-0348-7262-1_44.
Human coronary arteries were taken from heart transplant patients. Arteriosclerotic arteries were more depolarized and constricted over the whole PO2 range between 535 and 0 mm Hg. During oxygen deficiency, control preparations showed a maximal hyperpolarization of delta V = 10.9 mV and a maximal relaxation of delta T = 0.466 g. Arteriosclerotic arteries, however, became hyperpolarized by merely delta V = 7.1 mV and relaxed by delta T = 0.258 g. The isometric pretension was 2 g in all investigations. Two series of experiments, one with an application of indomethacin and another one with deendothelialized blood vessels, confirmed the hypothesis that the endothelium of arteriosclerotic coronary arteries arteries, indomethacin reduced the hypoxic hyperpolarization and dilatation at 30 mm Hg PO2 but about 51%. The reduction was 26% in arteriosclerotic vessels. The complete removal of the endothelium caused a 49% (74%) restriction of dilatory vascular reactivity. The relation was quite similar for a carbogen Krebs solution (resting, control conditions). The hyperpolarizing and dilatory contribution by prostacyclin was 32% in normal and 12% in arteriosclerotic coronaries. The rest can be attributed to the basal release of the endothelial dilator EDHR. Thus, it may be concluded that, in arteriosclerotic blood vessels, PGI2 synthesis and release are predominantly diminished or its effectivity is impaired. Finally we found the ratio PGI2/EDHF in the voltage and tension changes strongly shifted to the PGI2 side with a declining oxygen concentration. This is true for normal and arteriosclerotic vessels. In accordance with the activation curve for vascular smooth muscle, the hyperpolarization leads to relaxation via a closure of Ca2+ channels. 2.5 mV hyperpolarization reduces the tension developed by half.
取自心脏移植患者的人类冠状动脉。在535至0毫米汞柱的整个氧分压范围内，动脉粥样硬化动脉的去极化程度更高且收缩更明显。在缺氧期间，对照制剂显示最大超极化ΔV = 10.9毫伏，最大舒张ΔT = 0.466克。然而，动脉粥样硬化动脉仅超极化ΔV = 7.1毫伏，舒张ΔT = 0.258克。在所有研究中，等长预张力均为2克。两个系列的实验，一个应用消炎痛，另一个使用去内皮血管，证实了以下假设：动脉粥样硬化冠状动脉的内皮，消炎痛在30毫米汞柱氧分压时降低了缺氧超极化和扩张，但降低了约51%。在动脉粥样硬化血管中降低了26%。内皮的完全去除导致血管舒张反应性受限49%（74%）。对于加氧的克雷布斯溶液（静息、对照条件），情况非常相似。前列环素的超极化和舒张作用在正常冠状动脉中为32%，在动脉粥样硬化冠状动脉中为12%。其余可归因于内皮舒张因子EDHR的基础释放。因此，可以得出结论，在动脉粥样硬化血管中，前列环素（PGI2）的合成和释放主要减少或其有效性受损。最后，我们发现随着氧浓度降低，PGI2/内皮衍生超极化因子（EDHF）在电压和张力变化中的比值强烈向PGI2一侧偏移。正常和动脉粥样硬化血管均如此。根据血管平滑肌的激活曲线，超极化通过关闭Ca2+通道导致舒张。2.5毫伏的超极化使产生的张力减半。
