Effect of nitrite on endothelial function in isolated lung.

Area of Science:

• Biochemistry
• Physiology
• Pathology

Background:

• Nitrated tyrosine is linked to protein dysfunction and pathological processes.
• Angiotensin converting enzyme (ACE) dysfunction signifies endothelial injury.
• Nitrite exposure can exacerbate ACE dysfunction in cultured endothelial cells.

Purpose of the Study:

• To investigate if exogenous nitrite enhances endothelial ACE dysfunction in isolated rat lungs during polymorphonuclear neutrophil (PMN) activation.
• To determine the effect of nitrite on lung injury and nitrotyrosine levels.

Main Methods:

• Isolated rat lungs were perfused and treated with lipopolysaccharide (LPS).
• PMN activation was induced using formyl-Met-Leu-Phe (fMLP) or phorbol myristate acetate (PMA).
• ACE activity, vascular permeability, and nitrotyrosine immunoreactivity were measured with or without exogenous nitrite.

Main Results:

• Both fMLP and PMA reduced ACE activity and increased lung vascular permeability and pulmonary artery pressure.
• Exogenous nitrite did not potentiate the decrease in ACE activity or exacerbate lung injury.
• Nitrotyrosine immunoreactivity in lung homogenates was not increased by nitrite treatment.

Conclusions:

• In the whole isolated rat lung, exogenous nitrite does not worsen PMN-induced endothelial ACE dysfunction or lung injury.
• These findings suggest the presence of an endogenous factor in the rat lung that mitigates nitrated protein accumulation.
• This contrasts with observations in cultured endothelial cells, highlighting differences between in vitro and in vivo models.