Tang T, Joyner W L
Department of Physiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614-0002.
Microvasc Res. 1992 Jul;44(1):61-72. doi: 10.1016/0026-2862(92)90102-u.
Both in vitro and in vivo studies have revealed that removal of vascular endothelial cells abolishes the vasodilation to acetylcholine (Ach) but not sodium nitroprusside (SNP). Differential properties of endothelial cells in the series-arranged arterioles to vasodilator responses have not been studied. In this study, the cheek pouch microcirculation from the golden syrian hamster anesthetized with sodium pentobarbital (6 mg/100 g body wt, ip) was prepared for intravital microscopy. Measurements of lumen diameters of small series-arranged arterioles (2nd- and 4th-order) were made before, during, and after topical microapplication of different doses of either Ach or SNP. After control measurements, a light-dye (L-D) technique utilizing sodium fluorescein (FITC-dextran(150K), 50 mg/100 g body wt, iv) and illuminating a discrete area of the arteriole with 490-nm-wavelength light for 3 (4th) or 10 (2nd) min was used to impair endothelial cell function without damaging vascular smooth muscle cells. Responses to vasoactive substances for both 4th-order (10-20 microns) and second-order (30-50 microns) arterioles were retested. Vasodilatory responses to 10(-7) M Ach and SNP also were tested with and without the presence of NG-monomethyl L-arginine (L-NMMA), an inhibitor of EDRF/NO formation. In the control state, Ach and SNP produced a focal, dose-dependent increase in diameter in all arterioles tested. Endothelial impairment by L-D treatment significantly suppressed the vasodilator response to Ach in 4th- but not 2nd-order arterioles, whereas the SNP response was not significantly affected. Consistent with these observations, L-NMMA treatment significantly attenuated Ach-induced vasodilation in 4th-order arterioles, but it had no effect on 2nd-order arterioles. These studies document further the role of the endothelium in local modulation of arteriolar diameter in response to acetylcholine and demonstrate a differential effect for this response in series-arranged microvessels. Thus, there may be a heterogeneous distribution of endothelial cell functions for modulating vasodilator activity in microvessels.
体外和体内研究均表明，去除血管内皮细胞会消除对乙酰胆碱（Ach）的血管舒张反应，但不会消除对硝普钠（SNP）的反应。串联排列的小动脉中内皮细胞对血管舒张反应的差异特性尚未得到研究。在本研究中，制备了用戊巴比妥钠（6 mg/100 g体重，腹腔注射）麻醉的金黄叙利亚仓鼠的颊囊微循环，用于活体显微镜观察。在局部微量应用不同剂量的Ach或SNP之前、期间和之后，测量串联排列的小动脉（二级和四级）的管腔直径。在对照测量之后，使用一种光染料（L-D）技术，该技术利用荧光素钠（异硫氰酸荧光素葡聚糖（150K），50 mg/100 g体重，静脉注射），并用490纳米波长的光照射小动脉的一个离散区域3分钟（四级）或10分钟（二级），以损害内皮细胞功能而不损伤血管平滑肌细胞。对四级（10 - 20微米）和二级（30 - 50微米）小动脉对血管活性物质的反应进行重新测试。在有无NG-单甲基L-精氨酸（L-NMMA，一种内皮舒张因子/一氧化氮形成抑制剂）存在的情况下，也测试了对10⁻⁷ M Ach和SNP的血管舒张反应。在对照状态下，Ach和SNP在所有测试的小动脉中均产生了局部的、剂量依赖性的直径增加。L-D处理导致的内皮损伤显著抑制了四级小动脉对Ach的血管舒张反应，但对二级小动脉没有影响，而SNP反应未受到显著影响。与这些观察结果一致，L-NMMA处理显著减弱了四级小动脉中Ach诱导的血管舒张，但对二级小动脉没有影响。这些研究进一步证明了内皮在局部调节小动脉直径以响应乙酰胆碱方面的作用，并证明了在串联排列的微血管中这种反应存在差异效应。因此，在微血管中调节血管舒张活性的内皮细胞功能可能存在异质性分布。
