Markos F, Hennessy B A, Fitzpatrick M, O'Sullivan J, Snow H M
Department of Physiology, University College Cork, Ireland.
J Physiol. 2002 Nov 1;544(3):913-8. doi: 10.1113/jphysiol.2002.030478.
The effects of changes in the mean (S(m)) and pulsatile (S(p)) components of arterial wall shear stress on arterial dilatation of the iliac artery of the anaesthetized dog were examined in the absence and presence of the endothelin receptor antagonist tezosentan (10 mg kg(-1) I.V.; Ro 61-0612; [5-isopropyl-pyridine-2-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-(2-1H-tetrazol-5-yl-pyridin-4-yl)-pyrimidin-4-ylamide]). Changes in shear stress were brought about by varying local peripheral resistance and stroke volume using a distal infusion of acetylcholine and stimulation of the left ansa subclavia. An increase in S(m) from 1.81 +/- 0.3 to 7.29 +/- 0.7 N m(-2) (means +/- S.E.M.) before tezosentan caused an endothelium-dependent arterial dilatation which was unaffected by administration of tezosentan for a similar increase in S(m) from 1.34 +/- 0.6 to 5.76 +/- 1.4 N m(-2) (means +/- S.E.M.). In contrast, increasing the S(p) from 7.1 +/- 0.8 to a maximum of 11.5 +/- 1.1 N m(-2) (means +/- S.E.M.) before tezosentan reduced arterial diameter significantly. Importantly, after administration of tezosentan subsequent increases in S(p) caused arterial dilatation for the same increase in S(p) achieved prior to tezosentan, increasing from a baseline of 4.23 +/- 0.4 to a maximum of 9.03 +/- 0.9 N m(-2) (means +/- S.E.M.; P < 0.001). In conclusion, the results of this study provide the first in vivo evidence that pulsatile shear stress is a stimulus for the release of endothelin from the vascular endothelium.
在麻醉犬的髂动脉中，研究了动脉壁剪切应力的均值（S(m)）和脉动分量（S(p)）变化对动脉扩张的影响，研究分别在不存在和存在内皮素受体拮抗剂替唑生坦（10 mg kg(-1)静脉注射；Ro 61-0612；[5-异丙基-吡啶-2-磺酸 6-(2-羟基-乙氧基)-5-(2-甲氧基-苯氧基)-2-(2-1H-四氮唑-5-基-吡啶-4-基)-嘧啶-4-酰胺]）的情况下进行。通过使用乙酰胆碱远端输注和刺激左锁骨下袢来改变局部外周阻力和每搏输出量，从而引起剪切应力的变化。在替唑生坦给药前，S(m)从1.81±0.3增加到7.29±0.7 N m(-2)（均值±标准误）会引起内皮依赖性动脉扩张，而在替唑生坦给药后，当S(m)从1.34±0.6增加到5.76±1.4 N m(-2)（均值±标准误）时，这种扩张不受影响。相反，在替唑生坦给药前，S(p)从7.1±0.8增加到最大11.5±1.1 N m(-2)（均值±标准误）会显著减小动脉直径。重要的是，在替唑生坦给药后，随后S(p)的增加会引起动脉扩张，且扩张程度与替唑生坦给药前S(p)增加到相同水平时相同，即从基线4.23±0.4增加到最大9.03±0.9 N m(-2)（均值±标准误；P<0.001）。总之，本研究结果提供了首个体内证据，表明脉动剪切应力是血管内皮释放内皮素的刺激因素。
