RT Journal Article SR Electronic T1 Increased eNO and pulmonary iNOS expression in eNOS null mice JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 770 OP 773 DO 10.1183/09031936.03.00121203 VO 21 IS 5 A1 S. Cook A1 P. Vollenweider A1 B. Ménard A1 M. Egli A1 P. Nicod A1 U. Scherrer YR 2003 UL http://erj.ersjournals.com/content/21/5/770.abstract AB Nitric oxide (NO) is a major regulatory molecule of the cardiovascular system; however, measurement of vascular NO synthesis in vivo represents a major challenge. NO stemming from the lower respiratory tract has been used as a marker of vascular endothelial function. Experimental evidence for this concept is lacking. Therefore, the aim of the present study was to investigate this relationship. Lower respiratory tract exhaled NO concentration, together with systemic and pulmonary artery pressure, was measured in endothelial nitric oxide synthase (NOS) (eNOS) null mice (eNOS-/-). Similar studies were performed in inducible NOS (iNOS) null mice (iNOS-/-). Defective endothelial NO synthesis in eNOS-/- mice (evidenced by systemic and pulmonary hypertension) was associated with augmented exhaled NO levels (12.5±1.9 versus 9.8±1.2 parts per billion (ppb), eNOS-/- versus wild type), whereas normal endothelial NO synthesis in iNOS-/- mice was associated with decreased exhaled NO levels (4.3±1.5 ppb). Augmented exhaled NO levels in eNOS-/- mice were associated with upregulation of iNOS expression in the lung. These results indicate that inducible nitric oxide synthase is a major determinant of gaseous nitric oxide production in the lung, and lower respiratory tract exhaled nitric oxide does not always represent a marker of vascular endothelial nitric oxide synthesis. This study was supported by grants from the Swiss National Science Foundation (Bern, Switzerland), International Olympic Committee (Lausanne, Switzerland), Emma Muschamp Foundation (Lausanne) and Placide Nicod Foundation (Lausanne). This work was presented, in part, at the European Respiratory Society Annual Congress 2000, Florence, Italy, August 30–September 2, 2000, and at Experimental Biology 2001, Orlando, FL, USA, March 31–April 4, 2001.