Impairment of dilator responses of cerebral arterioles during diabetes mellitus: role of inducible NO synthase.

BACKGROUND AND PURPOSE 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. METHODS 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. RESULTS 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. CONCLUSIONS During diabetes, endothelial dysfunction of cerebral arterioles requires expression of iNOS and develops earlier than in carotid arteries.