Oxidative stress increases pulmonary capillary permeability in lean Zucker rats with chronic hyperglycemia (1153.6)

Abstract

Chronic hyperglycemia in obesity and diabetes is associated with increased vascular oxidative stress and endothelial dysfunction, including an increase in endothelial permeability. Increases in pulmonary capillary permeability associated with hyperglycemia and oxidative stress may contribute to lung edema in obesity and diabetes following trauma. We hypothesized that chronic hyperglycemia‐induced oxidative stress increases pulmonary capillary filtration coefficient (Kf). Lean Zucker rats (LZ) (n=12, STZ 50 mg/kg, ip) were hyperglycemia for 4 wks. A subgroup (n=6) was treated with apocynin (NADPH oxidase inhibitor, 2 mM in drinking water for 4 wks). Kf was measured in isolated lungs. Superoxide was measured in aortas using DHE. PMS (superoxide donor, 1 µM) was added to the isolated lung perfusate to determine the effect of an increased superoxide on Kf. Aortas from control LZ (LC) were treated with PMS to verify an increase in superoxide levels. STZ‐treated LZ (LS) exhibited significantly increased vascular superoxide levels and Kf (31 ± 4 ml/mmHg/g/min) compared to LC (7 ± 3 ml/mmHg/g/min). Apocynin treatment significantly reduced the superoxide levels and Kf (18 ± 3 ml/mmHg/g/min) in LS. PMS significantly increased Kf (37 ± 7 ml/mmHg/g/min) in isolated lungs from LC. These results suggest that, during chronic hyperglycemia, elevated vascular superoxide increases pulmonary permeability.Grant Funding Source: Supported by AHA‐12POST12060126, NIH HL‐51971, HL‐89581, and AHA‐12SDG12050525