白藜芦醇对大鼠离体胸主动脉环的舒张作用

目的:观察白藜芦醇(resveratrol,RVL)对大鼠离体胸主动脉血管的舒张作用并探讨其机制。方法:采用离体血管环灌流方法,观察RVL在含Ca²⁺或无Ca²⁺ Krebs液孵育条件下对去甲肾上腺素(NA)引起的血管平滑肌收缩的影响;同法观察RVL对30,80mmol·L^-1的KCl引起的血管平滑肌收缩的影响;RVL对NA引起的依赖于细胞内钙和细胞外钙收缩反应的影响,以及加入N-G-硝基-L-精氨酸(L-NNA)和优降糖后RVL舒张大鼠离体主动脉环效应的变化。结果:RVL呈浓度依赖性舒张NA引起的血管收缩;无Ca²⁺ 组RVL抑制NA所致血管平滑肌收缩效应大于含Ca²⁺ 组;RVL能够拮抗NA诱发的依内钙的收缩反应,而对外钙收缩无抑制。RVL对80,30mmol·L^-1 的KCl引起的血管平滑肌收缩均有抑制作用,且前者量效曲线明显上移。L-NNA使RVL舒血管效应降低(26.0±4.6)%;优降糖组的血管舒张受抑程度与对照组无显著差别(P>0.05)。结论:RVL可呈内皮依赖性舒张血管平滑肌,其作用机制可能与该药促进NO合成释放,开放钙激活的钾通道以及抑制血管平滑肌细胞外钙内流和内钙释放有关。

Effects of resveratrol on isolated thoracic aorta rings of rats

Objective: To investigate the relaxative characteristics of resveratrol on thoracic aortic artery in the rat and its mechanism. Method: We perfused the isolated rings and observed the response of NA-induced artery contraction to resveratrol under the Ca²⁺-contained and Ca²⁺ -free bath solutions. In the same way were the effect of reveratrol on the vascular smooth muscle observed by adding two different concentration of KC1 (30 and 80 mmol·L^-1) ,and the effect on the contraction of the vascular smooth muscle depending on the intracellular calcium and extracellular calcium were also observed by adding NA. We also observed the effect of resveratrol on the contraction of rings induced by NA in the presence of L-NNA and Glibenclamide. Result: Resveratrol relaxed rat aorta rings precontracted by NA in a dose-dependent manner. The relaxant effect of resveratrol on the rat rings of endothelium-denuded group was reduced compared with that of endothelium-intact group; the relaxant effect of resveratrol on rat rings was higher under the condition of Ca²⁺ -free bath solution than that under the condition of Ca²⁺-contained bath solution. Resveratrol had a repressive effect on the aorta's contraction induced by intracellular calcium, but had no effect induced by extracellular calcium. Resveratrol relaxed the contractions induced by KCl30 mmol· L^-1 as well as KCl 80 mmol·L^-1, but the contraction curve of KC1 80 mmol·L^-1 was shifted upward significantly. In the L-NNA group, the relaxant effect was attenuated by (26.0± 4.6) %; but there was no change in the group of Glibenclamide(P> 0.05). Conclusion: The results indicate that resveratrol relaxes vascular smooth muscle in an endothelium dependent manner. The mechanisms for this phenomenon seem to be related with promoting synthesis and release of NO, opening Ca²⁺ activated K⁺ channel (K_Ca, channel) as well as the inhibition of Ca²⁺ influx and release of Ca²⁺ from intracellular stores.