Increased Extravasation of Macromolecules in Skeletal Muscles of the Zucker Rat Model

Abstract

Assess whether changes in permeability of the muscle regional microcirculation occur in the obese Zucker rat model. Capillary permeability to albumin was assessed in vivo in Zucker rats (n = 15) and lean controls (n = 15) by quantifying the extravasation of albumin-bound Evans Blue (EB) in different organs. Unanaesthetized animals were injected with EB 20 mg/kg in the caudal vein, and EB was extracted by formamide from selected organs collected after exsanguination. Relative to control animals, Zucker rats had higher body weight (Delta = +33%; p < 0.001), plasma triglycerides (Delta = +244%; p < 0.001), and insulin (Delta = +240%; p < 0.001) concentrations. Plasma glucose concentrations were not different between the two groups (p = not significant). Using the EB technique, we showed a 30% to 50% (p < 0.01) increase in the extravasation of EB in the obese rats, regardless of the skeletal muscle group studied. This increase in skeletal muscle vasopermeability was not paralleled by any increase in the expression of the muscle endothelium-nitric oxide (NO) system because the total NO synthase (NOS) activity in skeletal muscle of the obese Zucker rat was significantly lower (p < 0.001), as was the endothelial NOS immunoreactive mass (p < 0.001), compared with lean controls. In conclusion, there seems to be dissociation between capillary permeability and local regulation of microcirculation in skeletal muscles of the obese Zucker rat. It is suggested that the increase in skeletal muscle vasopermeability (extravasation of macromolecules) is a compensation for the loss of NO-dependent vasodilation and capillary recruitment noted in this model of obesity and insulin resistance.