Brondum E, Kold-Petersen H, Nilsson H, Flyvbjerg A, Aalkjaer C
The Water and Salt Research Center, Institute of Physiology and Biophysics, University of Aarhus, DK-8000 Aarhus C, Denmark.
J Physiol Sci. 2008 Oct;58(5):333-9. doi: 10.2170/physiolsci.RP010108. Epub 2008 Oct 7.
Type 2 diabetes is associated with many circulatory manifestations, including alteration in endothelial function and hypertension. In this study we investigate the morphology and contractile response as well as the endothelial function of resistance arteries from the spontaneously diabetic Goto-Kakizaki (GK) rat, a model of lean type 2 diabetes expressing glucose intolerance.
Isolated mesenteric small arteries were investigated under isometric conditions in a wire myograph system using noradrenaline (NA) and the endothelium-dependent vasorelaxant acetylcholine (ACh). Media thickness was measured and media lumen ratio calculated.
No apparent morphological difference was noted between the arteries from GK rats and control Wistar (CW) rats. When exposed to the maximal NA concentration used (30 microM), arteries from GK rats developed significantly more tension than arteries from CW rats. In the presence of indomethacin (a specific blocker of the COX synthase) and of L-NAME (an inhibitor of eNOS), the response to NA was still significantly greater in GK rat arteries. Under control conditions, arteries from both groups showed intact relaxation to ACh. After incubation with indomethacin and L-NAME, both groups showed a non-NO nonprostaglandin-dependent relaxation to ACh. This relaxation could be blocked by a combination of apamin and charybdotoxin.
This study shows that mesenteric small arteries from the diabetic GK rat have increased contractile response to NA, along with a normal endothelial function and unaltered morphology.
2型糖尿病与许多循环系统表现相关，包括内皮功能改变和高血压。在本研究中，我们调查了自发性糖尿病Goto-Kakizaki（GK）大鼠（一种表现为葡萄糖不耐受的瘦型2型糖尿病模型）阻力动脉的形态、收缩反应以及内皮功能。
在等长条件下，使用去甲肾上腺素（NA）和内皮依赖性血管舒张剂乙酰胆碱（ACh），在血管张力测定系统中研究分离的肠系膜小动脉。测量中膜厚度并计算中膜腔径比。
GK大鼠的动脉与对照Wistar（CW）大鼠的动脉之间未观察到明显的形态学差异。当暴露于所用的最大NA浓度（30微摩尔）时，GK大鼠的动脉比CW大鼠的动脉产生的张力明显更大。在吲哚美辛（COX合酶的特异性阻滞剂）和L-NAME（eNOS抑制剂）存在的情况下，GK大鼠动脉对NA的反应仍然明显更大。在对照条件下，两组的动脉对ACh均表现出完整的舒张反应。在用吲哚美辛和L-NAME孵育后，两组对ACh均表现出非一氧化氮非前列腺素依赖性舒张。这种舒张可被蜂毒明肽和大蝎毒素的组合阻断。
本研究表明，糖尿病GK大鼠的肠系膜小动脉对NA的收缩反应增加，同时内皮功能正常且形态未改变。
