Hoeffner U, Vanhoutte P M
Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota.
Am J Hypertens. 1989 Oct;2(10):762-7. doi: 10.1093/ajh/2.10.762.
Experiments were designed to compare basal and acetylcholine-induced release of endothelium-derived relaxing factor at different flow rates in the aorta of the normotensive (Wistar-Kyoto; WKY) and spontaneously hypertensive (SHR) rat. Aortic segments (with endothelium) of either WKY or SHR were perfused at different flow rates (1 or 4 mL/min) with modified Krebs-Ringer solution; the relaxing activity of the perfusate from the two types of segments was bioassayed by measuring the isometric force in rings (without endothelium, and contracted with norepinephrine) of aortas of both WKY and SHR. All studies were performed in the presence of indomethacin to prevent endothelial production of prostacyclin and other vasodilator prostanoids. The basal release of endothelium-derived relaxing factor was not significantly affected by the flow rate in either the WKY or the SHR aortas. At the two flow rates, and with both types of bioassay rings, the basal release of endothelium-derived relaxing factor was smaller with SHR than with WKY aortas, but this reached significance only at 4 mL/min using the SHR-aorta as bioassay tissue. Both with WKY and SHR aortas the release of endothelium-derived relaxing factor evoked by acetylcholine was significantly larger at 1 than at 4 mL/min; no significant differences in responsiveness to acetylcholine were noted between WKY and SHR segments. There was also no difference in responsiveness of WKY and SHR bioassay rings to acetylcholine and acetylcholine-induced release of endothelium-derived relaxing factor. These experiments suggest that prolonged exposure to increases in shear stress reduces the ability of the endothelium to release endothelium-derived relaxing factor in responses to muscarinic activation.
实验旨在比较正常血压（Wistar-Kyoto；WKY）大鼠和自发性高血压（SHR）大鼠主动脉在不同流速下基础状态及乙酰胆碱诱导的内皮源性舒张因子释放情况。将WKY或SHR的主动脉段（带有内皮）以不同流速（1或4 mL/分钟）用改良的Krebs-Ringer溶液灌注；通过测量WKY和SHR主动脉环（无内皮，用去甲肾上腺素收缩）的等长力，对两种主动脉段灌注液的舒张活性进行生物测定。所有研究均在吲哚美辛存在的情况下进行，以防止内皮产生前列环素和其他血管舒张性前列腺素。内皮源性舒张因子的基础释放在WKY或SHR主动脉中均不受流速的显著影响。在两种流速下，使用两种类型的生物测定环，SHR主动脉中内皮源性舒张因子的基础释放均低于WKY主动脉，但仅在以SHR主动脉作为生物测定组织且流速为4 mL/分钟时，这一差异才具有统计学意义。对于WKY和SHR主动脉，乙酰胆碱诱发的内皮源性舒张因子释放在流速为1 mL/分钟时均显著大于4 mL/分钟；WKY和SHR主动脉段对乙酰胆碱的反应性未观察到显著差异。WKY和SHR生物测定环对乙酰胆碱及乙酰胆碱诱导的内皮源性舒张因子释放的反应性也没有差异。这些实验表明，长时间暴露于剪切应力增加的环境会降低内皮对毒蕈碱激活做出反应时释放内皮源性舒张因子的能力。
