摘要
目的研究17β-雌二醇(17β-estradiol,E2)是否通过钙激活钾通道(Kca)、ATP敏感钾通道(KATP)途径快速舒张人肠系膜动脉(human mesenteric artery,HMA)。方法采用离体血管环灌流方法,观察17β-雌二醇(E2)对内皮完整和去内皮HMA的舒张作用,以及左旋硝基精氨酸甲酯(L-NAME)、IBTX及格列苯脲(GLY)对这一过程的影响。结果E2(5×10-7～2×10-5mol/L)可剂量依赖性地快速舒张HMA;在低浓度(5×10-7～5×10-6mol/L)时,该舒张作用在内皮完整组明显大于去内皮组(P<0.05),且在内皮完整组E2的舒张作用可分别被一氧化氮合酶(NOS)选择性抑制剂L-NAME、大电导钙激活钾通道(BKca)阻断剂IBTX、ATP敏感钾通道(KATP)选择性抑制剂GLY减弱(P<0.05);在高浓度(10-5～2×10-5mol/L)时,去内皮组与内皮完整组E2的舒张反应差异无显著性(P>0.05),且阻断剂L-NAME、IBTX、GLY均不能削弱E2的舒张反应(P>0.05)。结论E2可以快速舒张人体阻力小血管——人肠系膜动脉,在低浓度时具有内皮依赖性,其舒张效应与刺激内皮释放NO和激活BKca、KATP有关,而在高浓度时E2舒张HMA是非内皮依赖的。
[ Objective ]To investigate the rapid vasorelaxing effects and mechanism of 17β-estrogen （E2） on human mesenteric arteries （HMA）. [ Methods ] HMA segments were harvested from humans during large intestine excision surgery. Patients with diabetes mellitus, hypercholesterolemia, hypertension, smoking habit, estrogen replacement therapy were excluded. The vasorelaxing effect of 17β-estradiol on artery rings from HMA with and without endothelium was measured by means of perfusion in vitro. Cumulative dose-response to 17β-estradiol in the range of 5×10^-7-2×10^-5 mol/L were observed in the presence and absence of Nω-nitro-L-arginine methyl ester （L-NAME, 100 μmol/L）, IBTX （100 nmol/L） and Glibenclamide （GLY, 10 μmol/L）. [ Result ] 17β-estradiol caused a concentration dependent rapid relaxtion on HMA. The vasorelaxation effect of 17β-estradiol at low level （5×10^-7-5×10^-6 mol/ L） was endothelium dependent, pretreatment with L-NAME, IBTX and GLY all attenuated this vasodilation effect. But 17β-estradiol at higher level （10^-5-2×10^-5 mol/L） induced endothelium independent vasorelaxation effect,and this vasodilation effect could not be attenuated by L-NAME, 1BTX and GLY. [Conclusion] 17β-estradiol on lower concentration results in an endothelium-dependent vasorelaxation of HMA by cliciting nitric oxide production and activation of BKCa or KATP channel. It also demonstrate that 17β-estradiol on higher concentration （10^-5～2×10^-5mol/L） results in an endothelium-independent vasodilation.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2009年第18期2768-2772,共5页
China Journal of Modern Medicine
