【摘要】 目的:研究早期糖尿病大鼠内皮依赖舒张反应（EDR）损伤的机制。方法:离体主动脉环张力实验。结果:乙酰胆碱（ACh）,组胺（His）,缓激肽,环匹阿尼酸（CPA）在糖尿病组EDR均比对照组明显减弱。而卡西霉素诱导的EDR未见损伤。L-NAME(0.3mmol·L^-1)预处理取消所有EDR,并使两组间效应均一化。ACh或CPA诱导最大EDR时,卡西霉素(1μmol·L^-1)进一步扩张糖尿病而非正常组血管环。硝普钠扩血管及CPA或His缩血管效应均无组间差异。结论:在4周链佐星糖尿病大鼠主动脉,受体而不是非受体介导的EDR普遍损伤,其机制与内皮细胞电容性钙内流信号通路受损从而使NO合成减少有关。更多还原

【Abstract】 AIM: To study whether impaired endothelium-dependent relaxation (EDR) in early diabetic mellitus in response to different receptor-mediated and nonreceptor-mediated vasodilators ran parallel and its possible mechanism. METHODS: Isometric tension recording in aortic rings from streptozotocin (Str)-induced diabetic and age-matched nondiabetic rats. RESULTS: EDR induced by receptor agonist acetylcholine (ACh), histamine (His) or bradykinin (BK) were all significantly reduced in diabetic rings compared with control rings, whereas nonreceptor agonist calcimycin-induced EDR was well reserved in diabetic rings [ IC50 control: (0.13 ± 0.07) μmol·L-1 diabetic: (0.14 ±0.06) μmol·L-1, P>0.05, n = 7]. Cyclopiazonic acid (CPA) which also is a non-receptor mediated endothelium-dependent vasorelaxant and cells’ capacitative Ca2+ entry stimulant, failed to trigger EDR in diabetic rings. Pretreatment with Nω-nitro-L-arginine methylester ( L-NAME, 0.3 mmol·L-1) not only abolished all of the EDR elicited by above mentioned vasodilators in either of diabetic or control rings, but also leveled responses triggered by each of the agonists between diabetic and control rings. Upon the maximal EDR induced by ACh (1 mol·L-1) or CPA (3 μmol·L-1) in phenylephrine (1 μmol·L-1) precontracted rings, calcimycin (1 μmol·L-1)further relaxed diabetic rings, but contracted control preparations. When endothelium was denuded, relaxation evoked by sodium nitroprusside and contractions triggered by CPA or His were all identical between diabetic and control rings. CONCLUSION: Receptor agonists but not nonreceptor agonists-induced EDR are commonly impaired in 4-wk Str-induced diabetic rat aorta, and this defective effect is attributable to the low formation of EDRF/NO which is related to impaired capacitative Ca2+ entry pathway in endothelium.更多还原