Effects of Acute and Chronic Hyperglycemia on Lung Capillary Permeability

Abstract

Hyperglycemia is correlated with increased vascular oxidative stress and increased vascular permeability. The role of acute and chronic hyperglycemia in affecting lung endothelial permeability is unclear in a type 2 diabetes setting. Lung capillary filtration coefficient (Kf) was measured in the isolated lung of lean Zucker (LZ) and obese Zucker rats (OZ). We hypothesized obesity increases lung vascular permeability through chronic hyperglycemia. OZ had impaired glucose and insulin tolerance which was associated with elevated lung Kf (19.4 ± 3 ml/mmHg/g/min) as compared to LZ (11.4 ± 2 ml/mmHg/g/min). In a separate experiment, OZ were subjected to 4 weeks of Metformin treatment (300 mg/kg/day orally) to improve insulin sensitivity. Metformin treatment improved oral glucose tolerance, insulin sensitivity, and vascular oxidative stress, and this was associated with improved baseline lung Kf (11.5 ± 1 ml/mmHg/g/min) as compared to OZ control animals. To examine the role of acute hyperglycemia in lung permeability, lungs from LZ and OZ were subjected to 30 minutes of an elevated glucose concentration (550 mg/dl). Acute hyperglycemia had no effect in OZ but increased lung Kf in LZ, which was ameliorated with acute antioxidant treatment (apocynin, 3mM) added to the lung perfusion solution. These data suggest that the chronic hyperglycemia in obesity can exacerbate lung vascular permeability, possibly through oxidative stress, and may blunt any further alterations in Kf during acute episodes hyperglycemia. This warrants further investigation into the use of antioxidants in the treatment of diabetic and acute hyperglycemic-induced lung hyperpermeability.