de Wit C, Schäfer C, von Bismarck P, Bolz S S, Pohl U
Institute of Physiology and Pathophysiology, Johannes-Gutenberg University Mainz, Duesbergweg 6, D-55099 Mainz, Germany.
Pflugers Arch. 1997 Aug;434(4):354-61. doi: 10.1007/s004240050408.
We studied whether a flow-independent increase of luminal wall shear stress (WSS) could dilate hamster arterioles in vivo and which endothelial mediators are potentially involved. To this end the plasma viscosity was elevated by exchanging blood for dextran-erythrocyte solution thereby augmenting WSS. Diameters of small and large arterioles as well as red blood cell velocities were measured before and after exchange of blood for solutions of identical haematocrit containing either high- (HMWD) or low-molecular weight dextran (LMWD). The potential role of endothelial autacoids was investigated by local application of the NO-synthase inhibitor NG-nitro-L-arginine (L-NNA), the inhibitor of cyclooxygenase, indomethacin (3 microM), or the K+-channel blocker, tetrabutylammonium (TBA, 0.1 mM) to assess the potential effects of EDHF. HMWD (n = 11 animals) increased plasma viscosity by 64 +/- 3% and dilated arterioles of all branching orders (A1-A4) significantly [by 24 +/- 3% (A1-A2) and 32 +/- 3% (A3-A4)]. This dilation compensated fully for the calculated initial increase of WSS. LMWD (n = 6) did not affect plasma viscosity or arteriolar diameters. Tissue treatment with L-NNA (30-300 microM, n = 12) substantially diminished the HMWD-induced dilation in small arterioles (A3-A4; to 13 +/- 3%; P<<0.05) and virtually abolished it in large ones (A1-A2). Consequently, the calculated WSS increased significantly in these arterioles (by 31 +/- 5%). TBA combined with L-NNA (n = 4) did not reduce further the remaining dilation. Indomethacin (n = 6) had no effect on HMWD-induced dilation. We conclude that an increase of WSS induces a mainly NO-mediated arteriolar dilation. This dilation occurs in all arteriolar branching orders and is of sufficient magnitude to compensate for the initial WSS-increase. Thus, any elevations of WSS fulfil the requirement for a signal to change diameter along the arteriolar tree in a coordinated manner. The fully compensating dilation which we observed indicates that WSS is a controlled variable. It does, however, raise questions as to its role as a continuous endothelial stimulus.
我们研究了管腔壁剪切应力（WSS）与血流无关的增加是否能在体内使仓鼠小动脉扩张，以及哪些内皮介质可能参与其中。为此，通过用葡聚糖 - 红细胞溶液置换血液来提高血浆粘度，从而增加WSS。在将血液置换为含有高（HMWD）或低分子量葡聚糖（LMWD）且血细胞比容相同的溶液之前和之后，测量小动脉和大动脉的直径以及红细胞速度。通过局部应用一氧化氮合酶抑制剂NG - 硝基 - L - 精氨酸（L - NNA）、环氧合酶抑制剂吲哚美辛（3 microM）或钾通道阻滞剂四丁基铵（TBA，0.1 mM）来研究内皮自分泌物质的潜在作用，以评估内皮衍生超极化因子（EDHF）的潜在影响。HMWD（n = 11只动物）使血浆粘度增加了64±3%，并使所有分支等级（A1 - A4）的小动脉显著扩张[（A1 - A2）扩张24±3%，（A3 - A4）扩张32±3%]。这种扩张完全补偿了计算得出的WSS的初始增加。LMWD（n = 6）对血浆粘度或小动脉直径没有影响。用L - NNA（30 - 300 microM，n = 12）进行组织处理显著减弱了HMWD诱导的小动脉（A3 - A4）扩张（降至13±3%；P << 0.05），并几乎消除了大动脉（A1 - A2）的扩张。因此，这些小动脉中计算得出的WSS显著增加（增加31±5%）。TBA与L - NNA联合使用（n = 4）并未进一步降低剩余的扩张。吲哚美辛（n = 6）对HMWD诱导的扩张没有影响。我们得出结论，WSS的增加主要诱导了一氧化氮介导的小动脉扩张。这种扩张发生在所有小动脉分支等级中，并且幅度足以补偿WSS的初始增加。因此，WSS的任何升高都满足了沿小动脉树协调改变直径的信号要求。我们观察到的完全补偿性扩张表明WSS是一个受控变量。然而，这确实引发了关于其作为持续内皮刺激物的作用的问题。
