17β-雌二醇对离体大鼠冠状动脉张力的影响及其机制

Effects of 17β-estradiol on isolated rat coronary artery tension and its mechanisms

目的观察17β-雌二醇对离体大鼠冠状动脉张力的影响及其机制。方法采用离体血管张力实验方法,大鼠冠状动脉环的张力舒缩状态采用PowerLab和DMT系统记录。用10-6mol/L苯肾上腺素预收缩血管,血管内皮完整与否用10-6mol/L乙酰胆碱对血管环是否有舒张来判断。观察17β-雌二醇对内皮完整及去内皮大鼠冠状动脉血管张力的影响,以及内皮型一氧化氮合酶抑制剂左旋硝精氨酸甲酯、鸟苷酸环化酶抑制剂亚甲蓝、钙激活钾通道阻断剂四乙胺、ATP敏感钾通道的阻断剂格列本脲、L-型钙通道激动剂(-)BayK8644及雌激素受体阻断剂ICI182780对这一过程的影响。用最大舒张率判断药物的作用,即加药后与加药前收缩幅度的百分比。结果 17β-雌二醇可引起内皮完整的冠状动脉浓度依赖性的舒张反应,去内皮后最大舒张率显著降低(P<0.05)。左旋硝精氨酸甲酯和亚甲蓝均可抑制17β-雌二醇的舒血管作用,显著降低了冠状动脉环的最大舒张率(P<0.05);四乙胺、格列本脲、(-)BayK8644可以使17β-雌二醇对冠状动脉的舒张作用减弱(P<0.05);雌激素受体特异性阻断剂ICI182780对此作用无显著影响(P>0.05)。结论 17β-雌二醇可引起内皮依赖性的冠状动脉舒张,其作用与一氧化氮合酶/一氧化氮系统激活、钙激活钾通道和ATP敏感钾通道开放、钙通道抑制有关,但与雌激素受体无关。

Objective To explore the relaxing effects of 17β-estradiol on isolated rat coronary artery tension and its mechanisms. Methods The tension of isolated rat coronary artery ring was measured by PowerLab and DMT systems. In vitro vascular perfusion with 10^-6 mol/L phenylephrine was adopted to pre-contract the vessels. The relaxing effects of acetylcholine （ 10^-6 mol/L） on vascular rings were taken as the standard to judge whether the blood vessel endothelium was intact. The effects of 17β-estradiol on isolated coronary artery tension in intact coronary artery rings and endothelinm-removed coronary artery rings of rats were observed. The influences of Nω- nitro-L-arginine methylester（ L-NAME, a nitric oxide synthase inhibitor）, methylene blue（ a guanylate cyclase inhibitor）, tetraethylam- monium （a calcium-activated potassium channel blocker）, glibenclamide （an ATP-sensitive potassium channel blocker）, （-） BayK8644 （a L-type calcium channel agonist） and ICI182780 （an estrogen receptor antagonist） in the procedure were observed. The effects of all drugs on vascular ring were presented by the maximum diastolic rate（the percentage of contraction extent before and after administration）. Results The 17β-estradiol induced a concentration-dependent relaxation in intact coronary artery rings, while the maximum diastolic rate of vessels without endothelium was significantly lower than that in vessels with intact endothelium（P 〈0.05）. L-NAME and methylene blue inhibited the relaxing effects of 17β-estradiol on the coronary artery,which obviously decreased the maxi- mum relaxing rate of coronary artery rings in both groups （P 〈 0.05 ）. Tetraetbylammonium, glibenelamide and （ - ）BayK8644 also re- duced the relaxing effects of 17 β-estradiol（P 〈 0.05）, whereas ICI182780 had no obvious effect on the relaxing effects of 17β-estradi- ol. Conclusion Th17β-estradiol can induce endothelium-dependent relaxation of coronary artery,which is related to the activation of nitric oxide synthase/nitric oxide, calcium-activated potassium channel and ATP-sensitive potassium channel, and the suppression of calcium channel, but has nothing to do with the estrogen receptor.