摘要
目的观察NO对血管紧张素Ⅱ介导的入球动脉收缩功能的影响，探讨其机制。方法使用分离的微灌注的入球动脉行等张收缩试验，给予L-NAME及血管紧张素Ⅱ等血管活性物质，观察入球动脉内径的变化。利用NO荧光探针DAF-FM观测入球动脉内皮NO释放情况。结果L-NAME（10μmol／L）时间依赖性的引起入球动脉的收缩，作用60min后动脉内径减少了35．2％。在灌注状态下，内皮NO荧光强度持续增加，60min后达70％；L-NAME明显抑制内皮NO的释放速率（从29％降到5．7％）。血管紧张素Ⅱ（10^-14-10^-6 mol／L）浓度依赖性的引起入球动脉收缩，最大收缩强度达41％；L-NAME预处理能够增强入球动脉对于AngⅡ的收缩反应，10^-10 mol／L AngⅡ收缩动脉直径达46％（没有L-NAME时为8．5％），10^-8 mol／L时为66％（没有L-NAME时为41％）。结论灌注产生的血管剪切力是刺激NO释放的重要因素，内皮功能的完整性及NO在调控AngⅡ介导的入球动脉收缩方面发挥重要的作用，NO生物利用度下降可能是肾脏疾病时入球动脉阻力增高的重要机制。
Objective To evaluate the influence of nitric oxide （NO） production on angiotensin Ⅱ （ Ang Ⅱ ） induced contraction of afferent arterioles, and understand the underlying mechanism. Methods Isolated afferent arterioles from wild-type mice were perfused to determine isotonic contractions. The diameter changes were observed during administration of various vasoactive substances, such as L-NAME and Ang Ⅱ. NO release of endothelial cells of afferent arterioles was measured using a fluorescence indicator for NO, DAF-FM. Results L-NAME （10^-4 mol/L） treatment induced contraction of afferent arterioles in a time-dependent manner. Basal diameter was decreased by 35.2 % after 60 minutes. On baseline perfusion, the fluorescence intensity of NO was gradually increased up to 70 % after 60 minutes. L-NAME treatment significantly inhibited NO release, which declined from 29 % to 5.7 %. Angiotensin Ⅱ （ Ang Ⅱ ） （ 10^-14 - 10^-6 mol/L） induced constrictions with dose-dependence. The maximum contraction treated with Ang Ⅱ was 41 % of baseline. Pretreatment with L-NAME enhanced contractile response of afferent arterioles to Ang Ⅱ. In the presence of L-NAME, 10^-10 mol/L and 10^-8 mol/L of Ang Ⅱ resulted in contraction of afferent arterioles respectively up to 46 % and 66 % （P 〈0. 05）, but only 8.5 % and 41% if L-NAME pretreatment was not given （P 〈 0. 05 ） . Conclusion The vascular shear stress induced by perfusion is the crucial factor in mediating NO release of endothelial cells, The integrality of endothelial cells and basal NO concentration play important roles in the control of afferent arterioles tone, and may be involved in counteracting the contractile responses to Ang Ⅱ. NO deficiency is probably the important mechanism thereby increasing afferent arterioles resistance in renal diseases.
出处
《医学分子生物学杂志》
CAS
CSCD
2008年第5期412-417,共6页
Journal of Medical Molecular Biology
