Inhaled nitric oxide does not reduce systemic vascular resistance in mice

Area of Science:

• Cardiovascular Physiology
• Pulmonary Medicine
• Pharmacology

Background:

• Inhaled nitric oxide (NO) is a selective pulmonary vasodilator.
• Previous studies suggested inhaled NO might cause systemic vasodilation when endogenous nitric oxide synthase (NOS) is inhibited.
• This raised questions about the systemic effects of NO absorption via the lungs.

Purpose of the Study:

• To investigate the systemic vascular effects of inhaled NO in mice.
• To determine if inhaled NO reduces systemic vascular resistance in the absence of endothelial NOS (NOS3).

Main Methods:

• Studied wild-type mice treated with a NOS inhibitor (N-nitro-L-arginine methyl ester) and NOS3-deficient mice.
• Measured cardiac output, left ventricular function, and systemic vascular resistance under anesthesia.
• Assessed blood pressure and heart rate in awake mice using tail-cuff and telemetric methods.

Main Results:

• Inhaled NO (80 ppm) did not alter cardiac output, left ventricular function, or systemic vascular resistance in anesthetized mice of either genotype.
• Breathing NO did not affect blood pressure or heart rate in awake wild-type or NOS3-deficient mice.
• No systemic vasodilating effect was observed, regardless of NOS inhibition or congenital absence of NOS3.

Conclusions:

• Absorption of NO or its adducts during inhalation is insufficient to induce systemic vasodilation in mice.
• The findings challenge the hypothesis that endogenous NOS inhibition uncovers a systemic vasodilating effect of inhaled NO in this model.