Popp R, Fleming I, Busse R
Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Franfurt, Germany.
Circ Res. 1998 Apr 6;82(6):696-703. doi: 10.1161/01.res.82.6.696.
To date, the release of the endothelium-derived hyperpolarizing factor (EDHF) has been demonstrated only in response to receptor-dependent Ca2+-elevating agonists. Since endothelial cells in situ are continuously subjected to rhythmic distension, we investigated the effect of rhythmic stretch on the release of EDHF from isolated porcine coronary arteries. In the combined presence of diclofenac and N(G)-nitro-L-arginine (L-NNA), sinusoidal pressure oscillations (from 40 to 50 mm Hg, 4 minutes, 1.5 Hz) led to simultaneous oscillations in the external diameter of coronary artery segments, the amplitude of which were decreased by iberiotoxin and apamin and also by endothelial denudation. In order to directly demonstrate the release of EDHF, the intraluminal solution from endothelium-intact coronary segments exposed to pulsatile stretch was applied to detector rat aortic smooth muscle cells, the membrane potential of which was continuously measured using the patch-clamp technique. The hyperpolarization of detector cells induced by the intraluminal solution was proportional to the amplitude of the pressure oscillations applied to the donor artery and was attenuated by either preincubation of donor arteries with 17-octadecynoic acid or application of either tetrabutylammonium or iberiotoxin to detector cells. In contrast to the bradykinin-induced release of EDHF, the EDHF synthesized in response to pulsatile stretch did not exhibit any tachyphylaxis. These findings demonstrate for the first time that the synthesis of EDHF in coronary arteries can be mechanically stimulated by rhythmic vessel wall distension and suggest that the continuous release of EDHF may contribute to the adjustment of an adequate vascular compliance and to the control of coronary blood flow.
迄今为止，内皮源性超极化因子（EDHF）仅在对受体依赖性Ca2+升高激动剂的反应中被证明会释放。由于原位内皮细胞不断受到节律性扩张，我们研究了节律性拉伸对分离的猪冠状动脉中EDHF释放的影响。在双氯芬酸和N(G)-硝基-L-精氨酸（L-NNA）共同存在的情况下，正弦压力振荡（40至50毫米汞柱，4分钟，1.5赫兹）导致冠状动脉段外径同时振荡，其振幅被iberiotoxin、蜂毒明肽以及内皮剥脱降低。为了直接证明EDHF的释放，将暴露于搏动性拉伸的完整内皮冠状动脉段的管腔内溶液应用于检测大鼠主动脉平滑肌细胞，使用膜片钳技术连续测量其膜电位。管腔内溶液诱导的检测细胞超极化与施加于供体动脉的压力振荡幅度成正比，并被供体动脉预先用17-十八炔酸孵育或向检测细胞施加四丁基铵或iberiotoxin所减弱。与缓激肽诱导的EDHF释放相反，响应搏动性拉伸合成的EDHF没有表现出任何快速耐受。这些发现首次证明冠状动脉中EDHF的合成可被节律性血管壁扩张机械刺激，并表明EDHF的持续释放可能有助于调节适当的血管顺应性和控制冠状动脉血流。
