Arteriolar smooth muscle responses are modulated by an intramural diffusion barrier.
Arteriolar smooth muscle responses are modulated by an intramural diffusion barrier.
复制标题
小动脉平滑肌反应由壁内扩散屏障调节。
DOI：
10.1152/ajpheart.1989.257.1.h10
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Duling,BR
中科院分区：
文献类型：
--
作者：
Lew,MJ;Rivers,RJ;Duling,BR
从仓鼠颊囊分离直径40~80微米的小动脉，两端插管，注入3-(N-吗啉)丙磺酸(MOPS)缓冲生理盐液(PSS)。用倒置显微镜和视频系统观察血管，测量微动脉直径。研究发现，小动脉对α1肾上腺素受体激动剂苯肾上腺素的反应在外膜表面应用时比在管腔表面应用时高100倍。相比之下，SKF 89748-A，也是一种α1-肾上腺素能受体选择性激动剂，但具有比苯肾上腺素更大的脂溶能力，在小动脉的任一表面都是等效性的。我们推测，这两种药物之间的差异是由于SKF 89748-A具有脂溶性，能够穿透小动脉壁中的扩散屏障。为了验证这一假设，我们测试了具有不同作用部位和脂类溶解度的一系列拮抗剂。α-肾上腺素能受体拮抗剂酚妥拉明和苯妥拉明以及毒扁豆碱受体拮抗剂阿托品、东莨菪碱和甲基托拉明均被发现与激动剂作用于小动脉的同一表面时，阻断激动剂的作用比作用于相反表面时更强。测量了每种化合物的辛醇-水分配系数，发现这些系数与所测试的每种药物的管腔效力与外膜效力的比率高度相关。这些数据支持这样的假设，即这些小动脉中的内皮细胞层形成了一种屏障，阻止了小的、水溶性的分子从管腔向平滑肌细胞层的扩散。这种屏障可能会对小动脉的反应性产生重大影响。
Arterioles (40–80 micron diameter) were isolated from the hamster cheek pouch, cannulated at both ends, and perfused with 3-(N-morpholino)propanesulfonic acid (MOPS)-buffered physiological salt solution (PSS). The vessels were observed with an inverted microscope and video system, and arteriolar diameter was measured. Arterioles were found to be 100 times more responsive to the alpha 1-adrenoceptor agonist phenylephrine when applied to the adventitial surface than when applied to the luminal surface. In contrast, SKF 89748-A, also an alpha 1-adrenoceptor selective agonist, but with a much greater lipid solubility than phenylephrine, was equipotent from either surface of the arteriole. We hypothesized that the difference between the two drugs was due to the ability of SKF 89748-A to permeate a diffusion barrier in the arteriolar wall because of its lipid-solubility. To test this hypothesis, a spectrum of antagonists with different sites of action and lipid solubilities was tested. The alpha-adrenoceptor antagonists phentolamine and benextramine and the muscarinic receptor antagonists atropine, scopolamine, and methscopolamine were all found to be more potent at blocking the action of appropriate agonists when applied to the same surface of the arteriole as the agonist than when applied to the opposite surface. Octanol-water partition coefficients were measured for each of the compounds, and these were found to be highly correlated with the ratio of luminal potency to adventitial potency for each of the drugs tested. These data support the hypothesis that the endothelial cell layer in these arterioles forms a barrier to the diffusion of small, water-soluble molecules from the lumen to the smooth muscle cell layer. Such a barrier may have a significant effect on arteriolar reactivity.