Nitric oxide (NO) is endogenously synthesized by nitric oxide synthases (NOSs) which convert L-arginine to L-citrulline and NO in the presence of oxygen and several cofactors. Once produced, NO is freely diffusible and enters target cells and into the airway and can be detected in exhaled breath of all humans. NO is formed in high concentrations in the upper respiratory tract (nasopharynx and paranasal sinuses). Our studies have also conclusively demonstrated that the lower respiratory tract is a significant source of NO in exhaled breath. We have also demonstrated that endogenous NO levels in the lung change rapidly in direct proportion to inspired oxygen which strongly supports a critical role for NO as mediator of ventilation-perfusion coupling in the lung.
NO also plays a major role in the pathophysiology of pulmonary hypertension (PH), a group of diseases characterized by high pulmonary artery pressures and pulmonary vascular resistance. Our studies have shown that patients with idiopathic pulmonary arterial hypertension (IPAH, previously known as primary pulmonary hypertension or PPH) have low levels of NO in their exhaled breath that increase after initiation of vasodilator therapy.
The goal of our current studies is to understand the role of nitric oxide (and other markers in exhaled breath) in lung physiology and in the pathophysiology of lung diseases like pulmonary hypertension and asthma.
Dweik RA, et.al. NO synthesis in the lung. JCI 1998. Dweik RA, et.al. NO Chemical Events in the Human Airway During Antigen-Induced Asthmatic Response. PNAS 2001. Dweik RA. Pulmonary hypertension and the search for the selective pulmonary vasodilator. Lancet 2002.Dweik RA. Nitric oxide, hypoxia, and superoxide: the good, the bad, and the ugly! Thorax 2005.(Dweik RA, contributing author). ATS Recommendations for Standardized Procedures for Exhaled Nitric Oxide 2005. AJRCCM 2005.Dweik RA. The lung in the balance: arginine, methylated arginines, and nitric oxide. AJP Lung 2007.