Hyperglycemia‐Mediated Oxidative Stress Increases Pulmonary Vascular Permeability

OBJECTIVE: Hyperglycemia in diabetes mellitus is associated with endothelial dysfunction as evidenced by increased oxidative stress and vascular permeability. Whether impaired glucose control in metabolic syndrome impacts pulmonary vascular permeability is unknown. We hypothesized that in metabolic syndrome, hyperglycemia increases lung vascular permeability through superoxide. METHODS: Lung capillary Kf and vascular superoxide were measured in the isolated lungs of LZ and OZ rats. OZ were subjected to 4 weeks of metformin treatment (300 mg/kg/day orally) to improve insulin sensitivity. In a separate experiment, lung vascular permeability and vascular superoxide were measured in LZ exposed to acute hyperglycemia (30 mM). RESULTS: As compared to LZ, OZ had impaired glucose and insulin tolerance and elevated vascular superoxide which was associated with an elevated lung Kf. Chronic metformin treatment in OZ improved glucose control and insulin sensitivity which was associated with decreased vascular oxidative stress and lung Kf. Acute hyperglycemia in isolated lungs from LZ increased lung Kf, which was blocked with the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin (3 mM). Apocynin also decreased baseline Kf in OZ. CONCLUSIONS: These data suggest that hyperglycemia in metabolic syndrome exacerbates lung vascular permeability through increases in vascular superoxide, possibly through NADPH oxidase.