Taddei S, Virdis A, Ghiadoni L, Magagna A, Favilla S, Pompella A, Salvetti A
Department of Internal Medicine, University of Pisa (Italy).
Hypertension. 2001 Mar;37(3):943-8. doi: 10.1161/01.hyp.37.3.943.
Essential hypertension is associated with impaired endothelium-dependent vasodilation caused by oxygen free radical-induced nitric oxide (NO) breakdown. Because calcium antagonists can improve endothelial function in patients with essential hypertension, in this study we tested the hypothesis that this beneficial effect could be related to restoration of NO availability by antioxidant properties. In 15 healthy subjects and 15 hypertensive patients, we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (ACh; 0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-dependent vasodilator in basal conditions, during infusion of N:(G)-monomethyl-L-arginine (L-NMMA, 100 microg/100 mL forearm tissue per minute), an NO-synthase inhibitor, vitamin C (8 mg/100 mL forearm tissue per minute), and finally, simultaneous infusion of L-NMMA and vitamin C. The response to sodium nitroprusside (SNP; 1, 2, and 4 microg/100 mL forearm tissue per minute) was also evaluated. In control subjects, vasodilation to ACh was inhibited by L-NMMA and not changed by vitamin C. In hypertensive patients, vasodilation to ACh was blunted as compared with control subjects and resistant to L-NMMA. Vitamin C, which decreased plasma isoprostanes and increased plasma antioxidant capacity, increased the response to ACh and restored the inhibiting effect of L-NMMA. In hypertensive patients, the study was repeated after 3-month treatment with nifedipine gastrointestinal therapeutic system (30 to 60 mg/daily). Nifedipine treatment decreased circulating plasma lipoperoxides and isoprostanes and increased plasma antioxidant capacity. Moreover, nifedipine increased the vasodilation to ACh but not to SNP and restored the inhibiting effect of L-NMMA on ACh-induced vasodilation, whereas vitamin C no longer exerted its facilitating activity. These results indicate that nifedipine increases endothelium-dependent vasodilation by restoring NO availability, an effect probably determined by antioxidant activity.
原发性高血压与氧自由基诱导的一氧化氮（NO）分解所导致的内皮依赖性血管舒张功能受损有关。由于钙拮抗剂可改善原发性高血压患者的内皮功能，在本研究中，我们检验了这样一个假设，即这种有益作用可能与通过抗氧化特性恢复NO的可用性有关。在15名健康受试者和15名高血压患者中，我们研究了在基础状态下，通过肱动脉内注入乙酰胆碱（ACh；0.15、0.45、1.5、4.5和15微克/100毫升每分钟）所诱导的前臂血流量（应变片体积描记法）变化，ACh是一种内皮依赖性血管舒张剂，在注入NO合酶抑制剂N：（G）-单甲基-L-精氨酸（L-NMMA，100微克/100毫升前臂组织每分钟）、维生素C（8毫克/100毫升前臂组织每分钟）期间，以及最后同时注入L-NMMA和维生素C期间。还评估了对硝普钠（SNP；1、2和4微克/100毫升前臂组织每分钟）的反应。在对照受试者中，L-NMMA抑制了对ACh的血管舒张反应，而维生素C对其无影响。与对照受试者相比，高血压患者对ACh的血管舒张反应减弱且对L-NMMA有抵抗性。维生素C降低了血浆异前列腺素水平并提高了血浆抗氧化能力，增加了对ACh的反应并恢复了L-NMMA的抑制作用。在高血压患者中，使用硝苯地平胃肠治疗系统（30至60毫克/每日）治疗3个月后重复该研究。硝苯地平治疗降低了循环血浆中的脂质过氧化物和异前列腺素水平，并提高了血浆抗氧化能力。此外，硝苯地平增加了对ACh的血管舒张反应，但对SNP无此作用，并恢复了L-NMMA对ACh诱导的血管舒张的抑制作用，而维生素C不再发挥其促进作用。这些结果表明，硝苯地平通过恢复NO的可用性增加内皮依赖性血管舒张，这一作用可能由抗氧化活性所决定。
