Kitayama Jiro, Faraci Frank M, Gunnett Carol A, Heistad Donald D
Cardiovascular Center and Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242-1081, USA.
Stroke. 2006 Aug;37(8):2129-33. doi: 10.1161/01.STR.0000231654.79017.df. Epub 2006 Jun 29.
During diabetes, expression of inducible nitric oxide synthase (iNOS) plays an important role in the development of endothelial dysfunction in extracranial blood vessels. Progression of vascular dysfunction after the onset of diabetes differs among vascular beds. In this study, the effects of hyperglycemia/diabetes on vasomotor function were examined in cerebral arterioles at 2 different times in control and iNOS-deficient mice and compared with the effects on carotid arteries.
Streptozotocin (150 mg/kg IP) was given to induce diabetes. The diameter of cerebral arterioles was measured through a cranial window in diabetic and nondiabetic mice in vivo. Vasomotor function of the carotid artery was examined in vitro.
In diabetic mice, responses of the cerebral arterioles to acetylcholine (1 mumol/L) were normal after 3 weeks of diabetes but were significantly impaired after 5 to 6 weeks of diabetes (4+/-1% [mean+/-SEM] increase in diameter) compared with control mice (14+/-1; P=0.0002). Responses to sodium nitroprusside were similar in diabetic and nondiabetic mice at both time points. In contrast, the vasomotor function of the carotid artery was not affected after 5 to 6 weeks of diabetes. In diabetic iNOS-deficient mice, cerebral arteriolar vasomotor function was not impaired, even after 4 months of diabetes.
During diabetes, endothelial dysfunction of cerebral arterioles requires expression of iNOS and develops earlier than in carotid arteries.
在糖尿病期间，诱导型一氧化氮合酶（iNOS）的表达在颅外血管内皮功能障碍的发展中起重要作用。糖尿病发病后血管功能障碍的进展在不同血管床之间存在差异。在本研究中，在对照小鼠和iNOS缺陷小鼠的两个不同时间点检测了高血糖/糖尿病对脑微动脉血管舒缩功能的影响，并与对颈动脉的影响进行了比较。
给予链脲佐菌素（150mg/kg腹腔注射）诱导糖尿病。通过颅骨视窗在体内测量糖尿病小鼠和非糖尿病小鼠脑微动脉的直径。在体外检测颈动脉的血管舒缩功能。
在糖尿病小鼠中，糖尿病3周后脑微动脉对乙酰胆碱（1μmol/L）的反应正常，但糖尿病5至6周后与对照小鼠相比显著受损（直径增加4±1%[平均值±标准误]）（对照小鼠为14±1；P=0.0002）。在两个时间点，糖尿病小鼠和非糖尿病小鼠对硝普钠的反应相似。相比之下，糖尿病5至6周后颈动脉的血管舒缩功能未受影响。在糖尿病iNOS缺陷小鼠中，即使糖尿病4个月后脑微动脉血管舒缩功能也未受损。
在糖尿病期间，脑微动脉的内皮功能障碍需要iNOS的表达，且比颈动脉更早出现。
