Shen J Z, Zheng X F
Department of Pharmacology, Faculty of Medicine, Zhejiang University, Hangzhou 310031, China.
Zhongguo Yao Li Xue Bao. 1999 Sep;20(9):844-50.
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.
Isometric tension recording in aortic rings from streptozotocin (Str)-induced diabetic and age-matched nondiabetic rats.
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) mumol.L-1 diabetic: (0.14 +/- 0.06) mumol.L-1, P > 0.05, n = 7]. Cyclopiazonic acid (CPA) which also is a nonreceptor mediated endothelium-dependent vasorelaxant and cells' capacitative Ca2+ entry stimulant, failed to trigger EDR in diabetic rings. Pretreatment with N omega-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 mumol.L-1) in phenylephrine (1 mumol.L-1) precontracted rings, calcimycin (1 mumol.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.
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.
研究早期糖尿病时内皮依赖性舒张功能（EDR）对不同受体介导及非受体介导的血管舒张剂反应是否平行及其可能机制。
采用链脲佐菌素（Str）诱导的糖尿病大鼠及年龄匹配的非糖尿病大鼠的主动脉环进行等长张力记录。
与对照环相比，糖尿病环中由受体激动剂乙酰胆碱（ACh）、组胺（His）或缓激肽（BK）诱导的EDR均显著降低，而由非受体激动剂A23187诱导的EDR在糖尿病环中保留良好[IC50对照：（0.13±0.07）μmol·L-1，糖尿病：（0.14±0.06）μmol·L-1，P>0.05，n=7]。同样作为非受体介导的内皮依赖性血管舒张剂及细胞容量性Ca2+内流刺激剂的环匹阿尼酸（CPA）未能在糖尿病环中触发EDR。用Nω-硝基-L-精氨酸甲酯（L-NAME，0.3 mmol·L-1）预处理不仅消除了上述血管舒张剂在糖尿病环或对照环中引发的所有EDR，而且使糖尿病环和对照环中各激动剂触发的反应水平相当。在去氧肾上腺素（1 μmol·L-1）预收缩的环中，由ACh（1 μmol·L-1）或CPA（3 μmol·L-1）诱导的最大EDR时，A23187（1 μmol·L-1）进一步舒张糖尿病环，但使对照制剂收缩。当去除内皮后，糖尿病环和对照环中硝普钠引起的舒张及CPA或His引起的收缩均相同。
在4周龄Str诱导的糖尿病大鼠主动脉中，受体激动剂而非非受体激动剂诱导的EDR普遍受损，这种缺陷效应归因于内皮依赖性舒张因子/一氧化氮（EDRF/NO）生成减少，这与内皮中容量性Ca2+内流途径受损有关。
