Impaired microvascular responses to acute hyperglycemia in type I diabeticrats

Abnormal reactivity of resistance vasculature may induce long-term alterati ons 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 microsco py in the skeletal muscle of diabetic rat and is particularly interesting a s-it applies to an iterative, physiological stimulus. The study was conduct ed in 5-month-old rats, either nondiabetic (ND) or rendered diabetic (D) fo r 12 weeks (streptozotocin, 60 mg/kg, i.v.). Intravital microscopy was used to examine diameter and vasomotion changes in precapillary arterioles (< 2 0 mu m) in the spinotrapezius muscle of fasted, anesthetized rats, before a nd up to 60 min after infusion of glucose or isotonic saline. After intrave nous glucose infusion, a precapillary arteriolar vasoconstriction associate d with an increase in the number of arterioles presenting vasomotion were s een in ND rats. In contrast, no modification in either parameter was observ ed in D rats. Our results indicate that, microvessels react to acute change s in the metabolic environment such as induced by elevation of plasma gluco se. There was a complete loss of reactivity (vasoconstriction and vasomotio n) of precapillary arterioles to superimposed hyperglycemia in D rats. Acco rding to the "hemodynamic hypothesis", this impaired vasoconstriction could result in hyperperfusion of microvessels and subsequent microvascular dama ges which might contribute to the development of diabetic microangiopathy. (C) 1999 Elsevier Science Inc.