Pourageaud F, Freslon J L
Department of Pharmacology, Faculty of Pharmacy, University of Bordeaux II, France.
J Vasc Res. 1995 May-Jun;32(3):190-9. doi: 10.1159/000159093.
The study was designed to compare the effects of agonists and flow on endothelial reactivity in perfused coronary arteries of spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. To this end, coronary arteries were cannulated at both ends using an arteriograph system. In the absence of flow and under an intraluminal pressure of 30 mm Hg, SHR arteries had larger internal diameters compared to those of WKY rats (275 +/- 10 vs. 239 +/- 7 microns, p < 0.01). In preparations preconstricted with serotonin HT, concentration-effect curves were constructed by adding acetylcholine or bradykinin in the bath. On the other hand, the effect of a stepwise increase in intraluminal flow (50-450 microliters/min) of physiological salt solution was observed. Agonist-induced dilations were significantly smaller in arteries of SHRs compared to those of WKY rats. Starting flow at the plateau of constriction led to dilations that were also weaker in SHR compared to WKY vessels: 27 +/- 6 vs. 61 +/- 3, p < 0.001, when expressed as percentage of maximal initial constrictions. The maximal dilation induced by flow in SHR arteries was obtained for a greater value of shear stress compared to that determined in WKY preparations: 81 +/- 6 vs. 60 +/- 4 dyn/cm2, p < 0.01. After endothelium destruction, flow-induced dilation was totally abolished in SHR arteries but only reduced in those of WKY rats. Subsequent additions of sodium nitroprusside induced complete dilations in vessels from both strains. The same protocol was performed in arteries submitted to a perfusion pressure of 90 mm Hg. In these conditions, impairments of agonist- and flow-induced dilations were also evidenced in SHR arteries. These results show that both the endothelium-dependent dilation induced by acetylcholine or bradykinin and the flow-induced dilation are impaired in coronary arteries of SHRs compared to WKY rats. These alterations appear to be due to a deterioration of endothelial cell function in the presence of a normal reactivity of the smooth muscle cells.
本研究旨在比较激动剂和血流对自发性高血压大鼠（SHR）和Wistar-Kyoto（WKY）大鼠灌注冠状动脉内皮反应性的影响。为此，使用动脉造影系统在两端对冠状动脉进行插管。在无血流且腔内压力为30 mmHg的情况下，与WKY大鼠相比，SHR动脉的内径更大（275±10 vs. 239±7微米，p<0.01）。在用5-羟色胺预收缩的制剂中，通过向浴槽中添加乙酰胆碱或缓激肽构建浓度-效应曲线。另一方面，观察了生理盐溶液腔内血流逐步增加（50-450微升/分钟）的效果。与WKY大鼠相比，SHR动脉中激动剂诱导的舒张明显较小。在收缩平台期开始血流导致的舒张在SHR中也比WKY血管弱：以最大初始收缩的百分比表示时为27±6 vs. 61±3，p<0.001。与WKY制剂相比，SHR动脉中血流诱导的最大舒张在更大的剪切应力值时获得：81±6 vs. 60±4达因/平方厘米，p<0.01。内皮破坏后，SHR动脉中血流诱导的舒张完全消失，但WKY大鼠的动脉中仅减少。随后添加硝普钠可使两种品系的血管完全舒张。在灌注压力为90 mmHg的动脉中进行相同的方案。在这些条件下，SHR动脉中激动剂和血流诱导的舒张受损也得到证实。这些结果表明，与WKY大鼠相比，SHR冠状动脉中乙酰胆碱或缓激肽诱导的内皮依赖性舒张和血流诱导的舒张均受损。这些改变似乎是由于在平滑肌细胞反应性正常的情况下内皮细胞功能恶化所致。
