Naderali E K, Smith S L, Doyle P J, Williams G
Diabetes and Endocrinology Research Unit, Department of Medicine, University of Liverpool, UCD, Daulby Street, Liverpool L69 3GA, UK.
Clin Sci (Lond). 2001 Jan;100(1):55-60.
Resveratrol has been shown to induce vasorelaxation. In this study, we investigated the mechanism(s) of resveratrol-induced vasorelaxation in resistance mesenteric arteries from male lean and dietary-induced obese rats. Compared with lean rats, arteries from dietary-obese rats showed significant (P<0.001) endothelial dysfunction, as indicated by a decrease (>20%) in maximal acetylcholine-induced vasorelaxation. Resveratrol (5-35 micromol/l) induced concentration-dependent relaxation of mesenteric arteries preconstricted with noradrenaline (8 micromol/l) or KCl (125 mmol/l) from both lean and dietary-obese rats. There were no significant differences between the two groups, achieving a maximum relaxation of >95% at a concentration of 35 micromol/l. In noradrenaline-preconstricted arteries from lean rats, N(G)-nitro-L-arginine methyl ester (L-NAME; 100 and 300 micromol/l) caused a significant (P<0.01) concentration-dependent rightward shift in reseveratrol activity, with no effect on maximal responses. However, L-NAME (100 and 300 micromol/l) did not alter the effects of reseveratrol on arteries from dietary-obese rats, giving superimposed concentration-responses curves. Indomethacin was also ineffective in altering resveratrol activity in arteries from both lean and dietary-obese rats. In noradrenaline-precontracted arteries from dietary-obese rats, responses to resveratrol were not attenuated by endothelial denudation, indicating an action independent of the endothelium. This study indicates that: (a) the maximal effects of resveratrol on resistance arteries from lean and dietary-obese rats are not effected by endothelial dysfunction, and (b) the effects of resveratrol in lean animals (where endothelial function is not impaired), but not in dietary-obese rats, are mediated via NO.
白藜芦醇已被证明可诱导血管舒张。在本研究中，我们调查了白藜芦醇诱导雄性瘦型大鼠和饮食诱导肥胖大鼠的肠系膜阻力动脉血管舒张的机制。与瘦型大鼠相比，饮食诱导肥胖大鼠的动脉表现出显著的（P<0.001）内皮功能障碍，这表现为最大乙酰胆碱诱导的血管舒张降低（>20%）。白藜芦醇（5 - 35微摩尔/升）可诱导来自瘦型和饮食诱导肥胖大鼠的、用去甲肾上腺素（8微摩尔/升）或氯化钾（125毫摩尔/升）预收缩的肠系膜动脉产生浓度依赖性舒张。两组之间无显著差异，在35微摩尔/升的浓度下最大舒张率>95%。在瘦型大鼠用去甲肾上腺素预收缩的动脉中，N(G)-硝基-L-精氨酸甲酯（L-NAME；100和300微摩尔/升）导致白藜芦醇活性出现显著的（P<0.01）浓度依赖性右移，对最大反应无影响。然而，L-NAME（100和300微摩尔/升）并未改变白藜芦醇对饮食诱导肥胖大鼠动脉的作用，得到的是叠加的浓度-反应曲线。吲哚美辛对改变瘦型和饮食诱导肥胖大鼠动脉中的白藜芦醇活性也无效。在饮食诱导肥胖大鼠用去甲肾上腺素预收缩的动脉中，内皮剥脱并未减弱对白藜芦醇的反应，表明其作用不依赖于内皮。本研究表明：（a）白藜芦醇对瘦型和饮食诱导肥胖大鼠阻力动脉的最大作用不受内皮功能障碍影响；（b）白藜芦醇在瘦型动物（内皮功能未受损）中的作用是通过一氧化氮介导的，但在饮食诱导肥胖大鼠中并非如此。
