CKD is an important predictor of poor clinical outcomes after acute ischemic stroke. Proteinuria independently contributes to the increased risks of neurologic deterioration, mortality, and poor functional outcome, but the eGFR may not be relevant to these outcomes.

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Background and Purpose-Studies of peripheral arteries in hypercholesterolemic animals suggest that increased generation of superoxide contributes to endothelial dysfunction, especially in the presence of atherosclerotic lesions. We tested the hypothesis that vasomotor function is impaired in cerebral arterioles during hypercholesterolemia through a mechanism that involves oxidative stress. Methods-Apolipoprotein E-deficient (apoE Ϫ/Ϫ ) mice were fed a normal or a high-fat diet for Ͼ6 months. ApoE ϩ/Ϫ mice fed a normal diet were used as normocholesterolemic controls. Responses of cerebral arterioles were examined in open cranial windows in vivo in anesthetized mice. Results-In apoEϪ/Ϫ mice, intimal area was increased only in the proximal aorta on the normal diet and also markedly increased in the distal aorta on the high-fat diet. There were no increases in intimal area in the aortas of control mice or in the cerebral arterioles in any group. The dilator response of cerebral arterioles to ACh (10 mol/L) in control mice (26Ϯ4% increase in diameter) was reduced in apoE Ϫ/Ϫ mice on either the normal (13Ϯ2%) or the high-fat (13Ϯ3%) diet (PϽ0.05 vs control). NADPH (10 mol/L), a substrate for NADPH oxidase, produced dilator responses in control mice (8Ϯ4%) that were significantly increased in apoE Ϫ/Ϫ mice on the high-fat diet (16Ϯ2%, PϽ0.05 vs control). Tempol, a superoxide scavenger, and apocynin, an inhibitor of NADPH oxidase, significantly increased vasodilator responses to ACh and decreased vasodilation to NADPH in apoE Ϫ/Ϫ mice on the high-fat diet. Nitroprusside produced a similar dilatation in the cerebral arterioles of all groups. Conclusions-Hypercholesterolemia is associated with oxidative stress and endothelial dysfunction in cerebral arterioles, despite the absence of atherosclerotic lesions.

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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 mol/L) were normal after 3 weeks of diabetes but were significantly impaired after 5 to 6 weeks of diabetes (4Ϯ1% [meanϮSEM] increase in diameter) compared with control mice (14Ϯ1; Pϭ0.0002). 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. Key Words: endothelium Ⅲ diabetes mellitus Ⅲ cerebral circulation Ⅲ microcirculation Ⅲ carotid arteries H yperglycemia during diabetes mellitus is associated with endothelial dysfunction. Effects of the duration of hyperglycemia on the progression of vascular dysfunction have been studied in several vascular beds. In the rat aorta, impairment of endothelium-dependent vasodilation appears 1 to 2 months after induction of diabetes with streptozotocin and may be related in part to the accumulation of advanced glycosylation end-products (AGEs). 1 On the other hand, endothelial function in small resistance arterioles seems to be impaired earlier than in large arteries; eg, vascular dysfunction is observed in rat intestinal arterioles as early as 1 week after induction of diabetes. 2 In other small vessels, such as cremaster muscle and mesenteric arterioles, vascular dysfunction develops within Ϸ1 month of diabetes. [3][4][5][6][7][8] In another pathological condition, hyperhomocysteinemia, cerebral arterioles appear to be more susceptible than large arteries to endothelial dysfunction. 9,10 Recent evidence suggests that impaired endothelium-dependent relaxation during diabetes may be dependent, in part, on the expression of inducible nitric oxide synthase (iNOS). 11,12 Some studies also reported increased expression and activity of iNOS in the heart soon after the onset of diabetes. [13][14][15] We have reported that in the carotid artery, endothelial dysfunction is present in wild-type but not in iNOS-deficient mice after 4 to 6 months of diabetes. 12 The role of iNOS in the development of endothelial dysfunction in intracranial blood vessels during hyperglycemia is unclear. Thus, ...