Mayhan W G
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, NE 68198-4575, USA.
Brain Res. 1998 Feb 9;783(2):326-31. doi: 10.1016/s0006-8993(97)01387-5.
Diabetes mellitus produces abnormalities of the endothelium and impairs endothelium-dependent dilatation of large and small cerebral blood vessels. However, the effect of diabetes mellitus on cerebral vasoconstriction and the modulatory influence of nitric oxide on cerebral vasoconstriction is unclear. Thus, the first goal of this study was to examine the effect of diabetes mellitus on constrictor responses of the basilar artery in vivo. Our second goal was to examine a potential role for nitric oxide in modulating constrictor responses of the basilar artery. A craniotomy was performed over the ventral medulla to expose the basilar artery. The diameter of the basilar artery was measured using intravital microscopy in nondiabetic and diabetic (3-4 months after injection of streptozotocin; 50-60 mg/kg i.p.) rats in response to angiotensin II, arginine vasopressin, endothelin-1, and the thromboxane analogue, U-46619. Topical application of angiotensin II (10 and 100 nM) produced only minimal changes in diameter of the basilar artery which were similar in nondiabetic and diabetic rats (p>0.05). Arginine vasopressin (0.1 and 1.0 nM), endothelin-1 (10 and 50 nM), and U-46619 (10 and 100 nM) produced marked dose-related constriction of the basilar artery which also was similar in nondiabetic and diabetic rats (p>0.05). Next, we examine whether the synthesis/release of nitric oxide played a role in constriction of the basilar artery in response to the agonists. We found that L-NMMA (1.0 microM) did not alter constrictor responses of the basilar artery in nondiabetic and diabetic rats. Thus, responses of the basilar artery to important vasoactive agonists are not altered by diabetes mellitus. In addition, it does not appear that the synthesis/release of nitric oxide modulates constrictor responses of the basilar artery to angiotensin II, arginine vasopressin, endothelin-1 and U-46619. We suggest that preservation of vasoconstrictor responses, coupled with impaired vasodilator responses, may contribute to the pathogenesis of cerebrovascular abnormalities associated with diabetes mellitus.
糖尿病会导致血管内皮异常，并损害大脑大小血管的内皮依赖性舒张功能。然而，糖尿病对脑血管收缩的影响以及一氧化氮对脑血管收缩的调节作用尚不清楚。因此，本研究的首要目标是在体内研究糖尿病对基底动脉收缩反应的影响。我们的第二个目标是研究一氧化氮在调节基底动脉收缩反应中的潜在作用。在延髓腹侧进行开颅手术以暴露基底动脉。使用活体显微镜测量非糖尿病和糖尿病大鼠（注射链脲佐菌素后3 - 4个月；腹腔注射50 - 60 mg/kg）基底动脉的直径，以观察其对血管紧张素II、精氨酸加压素、内皮素 - 1和血栓素类似物U - 46619的反应。局部应用血管紧张素II（10和100 nM）仅使基底动脉直径产生微小变化，非糖尿病和糖尿病大鼠的变化相似（p>0.05）。精氨酸加压素（0.1和1.0 nM）、内皮素 - 1（10和50 nM）和U - 46619（10和100 nM）可使基底动脉产生明显的剂量相关收缩，非糖尿病和糖尿病大鼠的反应也相似（p>0.05）。接下来，我们研究一氧化氮的合成/释放是否在基底动脉对激动剂的收缩反应中起作用。我们发现L - NMMA（1.0 microM）并未改变非糖尿病和糖尿病大鼠基底动脉的收缩反应。因此，糖尿病不会改变基底动脉对重要血管活性激动剂的反应。此外，一氧化氮的合成/释放似乎并未调节基底动脉对血管紧张素II、精氨酸加压素、内皮素 - 1和U - 46619的收缩反应。我们认为，血管收缩反应的保留以及血管舒张反应的受损可能有助于糖尿病相关脑血管异常的发病机制。
