Increased eNO and pulmonary iNOS expression in eNOS null mice.

Area of Science:

• Cardiovascular Physiology
• Respiratory Medicine
• Nitric Oxide Biology

Background:

• Nitric oxide (NO) is crucial for cardiovascular regulation, but in vivo measurement of vascular NO synthesis is challenging.
• Lower respiratory tract exhaled NO has been proposed as a marker for vascular endothelial function.
• Experimental validation of this concept is limited.

Purpose of the Study:

• To investigate the relationship between lower respiratory tract exhaled NO and vascular endothelial NO synthesis.
• To determine if exhaled NO accurately reflects endothelial nitric oxide synthase (eNOS) activity in vivo.
• To elucidate the role of inducible nitric oxide synthase (iNOS) in pulmonary NO production.

Main Methods:

• Measurements of lower respiratory tract exhaled NO concentration in endothelial NOS (eNOS) null mice (eNOS-/-) and inducible NOS (iNOS) null mice (iNOS-/-).
• Simultaneous monitoring of systemic and pulmonary artery pressure in these mouse models.
• Assessment of iNOS expression in lung tissue of eNOS-/- mice.

Main Results:

• eNOS-/- mice with defective endothelial NO synthesis exhibited significantly augmented exhaled NO levels (12.5 +/- 1.9 ppb) compared to wild-type mice (9.8 +/- 1.2 ppb).
• iNOS-/- mice with normal endothelial NO synthesis showed decreased exhaled NO levels (4.3 +/- 1.5 ppb).
• Augmented exhaled NO in eNOS-/- mice correlated with increased iNOS expression in the lung.

Conclusions:

• Inducible nitric oxide synthase (iNOS) is a primary determinant of gaseous NO production in the lungs.
• Lower respiratory tract exhaled NO does not consistently serve as a marker for vascular endothelial NO synthesis.
• The study challenges the utility of exhaled NO as a sole indicator of endothelial function.