Kreidstein M L, Pang C Y, Carlsen L N, Xu N
Research Institute, Hospital for Sick Children, Toronto, Ont., Canada.
Can J Physiol Pharmacol. 1992 Sep;70(9):1208-16. doi: 10.1139/y92-168.
Acetylcholine (ACh) and nitroglycerin (NTG) were used as probes to study endothelium-dependent and endothelium-independent vascular relaxation in isolated perfused transverse paraumbilical human skin flaps. It was observed that ACh (10(-6) M) significantly (p < 0.05) decreased the vascular resistance and increased dermal capillary perfusion (assessed by surface fluorometry) in norepinephrine (NE, 10(-6) M) preconstricted skin flaps, despite the presence of a cyclooxygenase inhibitor (indomethacin, 3 x 10(-5) M) and a beta-adrenergic receptor antagonist (propranolol, 10(-6) M). The ability of ACh to induce vascular relaxation in NE-preconstricted skin flaps was lost after damaging the vascular endothelial lining with saponin perfusion (100 mg.L-1, 5 min). In contrast, NTG (10(-6) M) induced vascular relaxation to a similar extent before and after saponin treatment. In a separate study, ACh was seen to induce vascular relaxation in a concentration-dependent manner in skin flaps preconstricted with NE (10(-6) M). This vascular relaxation effect of ACh over the dose range of 10(-9)-10(-5) M was significantly (p < 0.01) inhibited in the presence of N omega-nitro-L-arginine (10(-5) M), a nitric oxide (NO) synthesis inhibitor. These observations were taken to indicate the presence of endothelium-dependent and endothelium-independent vascular relaxation in human skin flaps and that the ACh-induced endothelium-dependent relaxation is probably mediated by NO. The importance of impairment of endothelium-dependent relaxation in the pathogenesis of skin flap ischemia, and the potential use of topical nitrovasodilators or NO donors for prevention and (or) treatment of skin flap ischemia were also discussed.
以乙酰胆碱（ACh）和硝酸甘油（NTG）作为探针，研究离体灌注的人脐旁横形皮瓣中内皮依赖性和非内皮依赖性血管舒张作用。结果发现，在预先用去甲肾上腺素（NE，10⁻⁶ M）收缩的皮瓣中，尽管存在环氧化酶抑制剂（吲哚美辛，3×10⁻⁵ M）和β-肾上腺素能受体拮抗剂（普萘洛尔，10⁻⁶ M），ACh（10⁻⁶ M）仍能显著（p < 0.05）降低血管阻力并增加真皮毛细血管灌注（通过表面荧光测定法评估）。在用皂苷灌注（100 mg·L⁻¹，5分钟）破坏血管内皮后，ACh在NE预先收缩的皮瓣中诱导血管舒张的能力丧失。相比之下，NTG（10⁻⁶ M）在皂苷处理前后诱导血管舒张的程度相似。在另一项研究中，观察到ACh在预先用NE（10⁻⁶ M）收缩的皮瓣中以浓度依赖性方式诱导血管舒张。在存在一氧化氮（NO）合成抑制剂Nω-硝基-L-精氨酸（10⁻⁵ M）的情况下，ACh在10⁻⁹ - 10⁻⁵ M剂量范围内的这种血管舒张作用受到显著（p < 0.01）抑制。这些观察结果表明人脐旁横形皮瓣中存在内皮依赖性和非内皮依赖性血管舒张，并且ACh诱导的内皮依赖性舒张可能由NO介导。还讨论了内皮依赖性舒张受损在皮瓣缺血发病机制中的重要性，以及局部硝基血管扩张剂或NO供体在预防和（或）治疗皮瓣缺血中的潜在用途。
