PT  - JOURNAL ARTICLE
AU  - Cook, S.
AU  - Vollenweider, P.
AU  - Ménard, B.
AU  - Egli, M.
AU  - Nicod, P.
AU  - Scherrer, U.
TI  - Increased eNO and pulmonary iNOS expression in eNOS null mice
AID  - 10.1183/09031936.03.00121203
DP  - 2003 May 01
TA  - European Respiratory Journal
PG  - 770--773
VI  - 21
IP  - 5
4099  - http://erj.ersjournals.com/content/21/5/770.short
4100  - http://erj.ersjournals.com/content/21/5/770.full
SO  - Eur Respir J2003 May 01; 21
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.