Impaired microvascular responses to acute hyperglycemia in type I diabetic rats

Abnormal reactivity of resistance vasculature may induce long-term alterations in regional hemodynamics, contributing to the pathogenesis of diabetic microangiopathy. The purpose of this study was to examine the responses of microvessels to a hyperglycemic episode aimed at mimicking a physiological stimulus such as the postprandial state. This study is the first to report the direct, in situ, visualization of this situation by intravital microscopy in the skeletal muscle of diabetic rat and is particularly interesting as it applies to an iterative, physiological stimulus. The study was conducted in 5-month-old rats, either nondiabetic (ND) or rendered diabetic (D) for 12 weeks (streptozotocin, 60 mg/kg, i.v.). Intravital microscopy was used to examine diameter and vasomotion changes in precapillary arterioles (< 20 microm) in the spinotrapezius muscle of fasted, anesthetized rats, before and up to 60 min after infusion of glucose or isotonic saline. After intravenous glucose infusion, a precapillary arteriolar vasoconstriction associated with an increase in the number of arterioles presenting vasomotion were seen in ND rats. In contrast, no modification in either parameter was observed in D rats. Our results indicate that, microvessels react to acute changes in the metabolic environment such as induced by elevation of plasma glucose. There was a complete loss of reactivity (vasoconstriction and vasomotion) of precapillary arterioles to superimposed hyperglycemia in D rats. According to the "hemodynamic hypothesis", this impaired vasoconstriction could result in hyperperfusion of microvessels and subsequent microvascular damages which might contribute to the development of diabetic microangiopathy.