Impaired nitric oxide-mediated flow-induced dilation in arterioles of spontaneously hypertensive rats.
Impaired nitric oxide-mediated flow-induced dilation in arterioles of spontaneously hypertensive rats.
复制标题
自发性高血压大鼠小动脉中一氧化氮介导的血流诱导扩张受损。
DOI：
10.1161/01.res.74.3.416
复制
发表时间：
1994
影响因子：
20.1
通讯作者：
Huang,A
中科院分区：
文献类型：
--
作者：
Koller,A;Huang,A
我们检验了骨骼肌小动脉血流依赖性扩张机制受损是高血压患者外周阻力增加的潜在原因之一的假设。研究了12周龄自发性高血压（SH）和正常血压Wistar （NW）大鼠股薄肌分离的管状小动脉（约55微米）。在恒灌注压（80 mm Hg）条件下，NW和SH小动脉的主动直径分别为57.7 +/- 1.9和51.5 +/- 3.2微米，而无Ca（2+）溶液的被动直径分别为113.6 +/- 2.9和101.7 +/- 2.9微米。灌注液的流量以5微升/分钟的速度从0增加到25微升/分钟，引起血流诱导的扩张。与NW大鼠相比，SH小动脉的这种反应明显较少。例如，在25 μ l /min流速下，SH大鼠的小动脉直径比NW大鼠约小56% （P < 0.05）。吲哚美辛是一种前列腺素合成抑制剂，在两株大鼠中均显著减弱了血流-直径曲线。一氧化氮合酶抑制剂N - omega-硝基- l -精氨酸使NW大鼠的流量-直径曲线明显向右移动，但对SH大鼠的流量-直径曲线没有影响。因此，目前的研究结果表明，在正常血压大鼠的股薄肌小动脉中，当血流增加（剪切应力）时，前列腺素和一氧化氮共同释放，导致扩张。然而，在早期高血压中，由于一氧化氮介导的血流依赖性小动脉扩张部分受损，血流增加导致小动脉扩张减少。
We tested the hypothesis that impairment of flow-dependent dilator mechanisms of skeletal muscle arterioles is one of the underlying reasons for the increased peripheral resistance in hypertension. Isolated, cannulated arterioles (approximately 55 microns) of gracilis muscle of 12-week-old spontaneously hypertensive (SH) and normotensive Wistar (NW) rats were investigated. At a constant perfusion pressure (80 mm Hg), the active diameters of NW and SH arterioles were 57.7 +/- 1.9 and 51.5 +/- 3.2 microns, whereas their passive diameters (Ca(2+)-free solution) were 113.6 +/- 2.9 and 101.7 +/- 2.9 microns, respectively. Flow-induced dilation was elicited by increases in flow of the perfusion solution from 0 to 25 microL/min in 5-microL/min steps. This response was significantly less in arterioles of SH compared with NW rats. For example, at 25-microL/min flow, the diameter of arterioles of SH rats was approximately 56% less (P < .05) than those of NW rats. Indomethacin, an inhibitor of prostaglandin synthesis, significantly attenuated the flow-diameter curve in both strains of rats. In contrast, N omega-nitro-L-arginine, a nitric oxide synthase inhibitor, significantly shifted the flow-diameter curve to the right in NW rats, but it did not affect the flow-diameter curve in SH rats. Thus, the present findings demonstrate that in gracilis muscle arterioles of normotensive rats in response to increases in flow (shear stress), prostaglandins and nitric oxide are co-released, resulting in a dilation. In early hypertension, however, there is a reduced arteriolar dilation to increases in flow that is due to the impairment of the nitric oxide-mediated portion of the flow-dependent arteriolar dilation.