Brunner F, Hoffmann C, Schuller-Petrovic S
Department of Pharmacology and Toxicology, Karl-Franzens-Universität Graz, Graz, Austria.
Br J Clin Pharmacol. 2001 Mar;51(3):219-24. doi: 10.1046/j.1365-2125.2001.00334.x.
To test in vitro the constrictor and relaxation responsiveness of variously diseased segments of human saphenous vein from patients with varicose vein disease.
The vein segments were derived (i) from the inguinal saphenous vein (valvularly incompetent and slightly dilated; tissue A); (ii) from the distal end of the lower leg just above the medial ankle (competent; tissue B); (iii) from a tributary to the long saphenous vein just below the knee (dilated, incompetent and overtly varicose; tissue C). The contractile responses were tested with phenylephrine (an alpha-adrenergic receptor agonist) and aescin, a clinically used phlebotonic drug derived from horse chestnut extract. Relaxant responses were tested with acetylcholine and sodium nitroprusside.
Both contractile agents contracted vein segments from the inguinal and ankle area with similar potency and efficacy, but were virtually without effect in the overtly varicose segments from the calf. EC50 values (molar concentration of the agonist that produces 50% of the maximum effect) in tissues A and B were 2.9 +/- 0.3 and 2.5 +/- 0.5 micromol l(-1) (phenylephrine) and 9.4 +/- 1.0 and 15.9 +/- 2.5 micromol l(-1) (aescin); the corresponding maximum effects (maximum effect, percent of KCl-induced contraction) were 76 +/- 3 and 70 +/- 4% (phenylephrine) and 70 +/- 2 and 71 +/- 3% (aescin) (P = NS in both cases for A vs B). In tissue C, the maximum effects were 5 +/- 5% (phenylephrine) and 10 +/- 7% (aescin) of KCl-induced contraction (not significantly different from zero). Acetylcholine-induced relaxation was similar for vein segments from locations A and B, whereas sodium nitroprusside was more effective in tissue B than A.
These findings support the notion that abnormalities within the venous wall affect venous smooth muscle contractility. Since competent and incompetent clinically normal vessels show normal contractile responses, whereas varicose vessels are not responsive to vasoactive drugs, it is likely that pharmacological treatment regimens are effective in early, but not in late stages of the disease.
在体外测试患有静脉曲张疾病患者的大隐静脉不同病变节段的收缩和舒张反应性。
静脉节段取自：（i）腹股沟大隐静脉（瓣膜功能不全且轻度扩张；组织A）；（ii）小腿内侧踝关节上方的远端（功能正常；组织B）；（iii）膝关节下方大隐静脉的一条属支（扩张、功能不全且明显曲张；组织C）。用去氧肾上腺素（一种α-肾上腺素能受体激动剂）和七叶皂苷（一种临床使用的源自七叶树提取物的静脉活性药物）测试收缩反应。用乙酰胆碱和硝普钠测试舒张反应。
两种收缩剂使腹股沟和踝关节区域的静脉节段收缩，效力和效果相似，但对小腿明显曲张的节段几乎没有作用。组织A和B中去氧肾上腺素的EC50值（产生最大效应50%的激动剂摩尔浓度）分别为2.9±0.3和2.5±0.5 μmol l⁻¹，七叶皂苷的EC50值分别为9.4±1.0和15.9±2.5 μmol l⁻¹；相应的最大效应（最大效应，KCl诱导收缩的百分比）分别为76±3和70±4%（去氧肾上腺素）以及70±2和71±3%（七叶皂苷）（A与B比较，两种情况P均为无显著性差异）。在组织C中，最大效应分别为KCl诱导收缩的5±5%（去氧肾上腺素）和10±7%（七叶皂苷）（与零无显著差异）。乙酰胆碱诱导的舒张在组织A和B的静脉节段中相似，而硝普钠在组织B中比在组织A中更有效。
这些发现支持静脉壁内的异常会影响静脉平滑肌收缩性这一观点。由于功能正常和功能不全的临床正常血管显示出正常的收缩反应，而曲张血管对血管活性药物无反应，因此药物治疗方案可能在疾病早期有效，但在晚期无效。
