Impairment of endothelium-dependent dilatation of cerebral arterioles during diabetes mellitus

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Abstract
The goal of this study was to determine whether responses of cerebral arterioles to vasoactive substances released by platelets are altered during diabetes mellitus. To induce diabetes, rats were injected with streptozotocin (50-60 mg/kg ip). Rats were characterized as diabetic by a blood glucose of greater than 300 mg/dl. Diameter of pial arterioles was measured during superfusion with ADP, serotonin, and the thromboxane analogue (U-46619), with the use of intravital microscopy in control (non-diabetic) and diabetic rats. ADP (10(-5)M) increased pial arteriolar diameter by 13 +/- 1% (mean +/- SE) in control rats and did not change diameter of arterioles in diabetic rats (1 +/- 1%). Serotonin (10(-5)M) increased diameter of cerebral arterioles by 9 +/- 1% in control rats and constricted arterioles by 5 +/- 2% in diabetic rats. Nitroglycerin produced similar dilatation of cerebral arterioles in control and diabetic rats, suggesting that impaired dilatation of cerebral arterioles in diabetic rats was not related to nonspecific impairment of vasodilatation. The thromboxane analogue U-46619 produced similar constriction of cerebral arterioles in control and diabetic rats. Thus endothelium-dependent dilatation of cerebral arterioles in response to ADP and serotonin is profoundly impaired in diabetic rats.