Hyperglycemia-Mediated Oxidative Stress Increases Pulmonary Vascular Permeability

Area of Science:

• Cardiovascular Physiology
• Metabolic Disorders
• Pulmonary Medicine

Background:

• Diabetes mellitus-associated hyperglycemia impairs endothelial function, increasing oxidative stress and vascular permeability.
• The impact of impaired glucose control in metabolic syndrome on pulmonary vascular permeability remains unclear.

Purpose of the Study:

• To investigate if hyperglycemia in metabolic syndrome increases lung vascular permeability through superoxide production.
• To explore the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in this process.

Main Methods:

• Isolated rat lungs (lean Zucker [LZ] and obese Zucker [OZ] rats) were used to measure lung capillary filtration coefficient (Kf) and vascular superoxide.
• Obese Zucker rats received metformin to improve insulin sensitivity.
• Acute hyperglycemia was induced in LZ rats, and the effect of the NADPH oxidase inhibitor apocynin was assessed.

Main Results:

• Obese Zucker rats exhibited impaired glucose tolerance, elevated vascular superoxide, and increased lung Kf compared to lean Zucker rats.
• Metformin treatment improved glucose control and reduced vascular superoxide and lung Kf in obese Zucker rats.
• Acute hyperglycemia increased lung Kf in lean Zucker rats, an effect inhibited by apocynin. Apocynin also reduced baseline Kf in obese Zucker rats.

Conclusions:

• Hyperglycemia in metabolic syndrome exacerbates lung vascular permeability.
• Increased vascular superoxide, potentially mediated by NADPH oxidase, is implicated in this process.