Enhanced expression of inducible nitric oxide synthase without vasodilator effect in chronically infected lungs

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 277; no. 3; pp. 616 - L627
• Main Authors: Cadogan, Elaine, Hopkins, Natalie, Giles, Shay, Bannigan, John G, Moynihan, John, McLoughlin, Paul
• Format: Journal Article
• Language: English
• Published: United States 01.09.1999
• Subjects: Animals; Chronic Disease; Enzyme Inhibitors - pharmacology; In Vitro Techniques; Lung - drug effects; Lung - physiopathology; Male; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase - physiology; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Perfusion; Pressure; Pseudomonas Infections - enzymology; Pseudomonas Infections - physiopathology; Rats; Rats, Sprague-Dawley; Vasodilation
• ISSN: 1040-0605; 0002-9513; 1522-1504
• DOI: 10.1152/ajplung.1999.277.3.L616

Department of Human Anatomy and Physiology, University College, Dublin 2, Ireland We hypothesized that abnormal ventilation-perfusion matching in chronically infected lungs was in part due to excess nitric oxide (NO) production after upregulation of inducible NO synthase (iNOS) expression. Rats were anesthetized and inoculated intratracheally with Pseudomonas aeruginosa incorporated into agar beads (chronically infected) or with sterile agar beads (placebo inoculated) and killed 10-15 days later. Immunohistochemistry demonstrated increased expression of iNOS and reduced expression of endothelial NOS (eNOS) in chronically infected compared with placebo-inoculated or noninoculated lungs. In isolated lungs from chronically infected rats, NOS inhibition with N -nitro- L -arginine methyl ester increased the mean perfusion pressure (14.4 ± 2.7 mmHg) significantly more than in the placebo-inoculated (4.8 ± 1.0 mmHg) or noninoculated (5.3 ± 0.8 mmHg) lungs ( P  <   0.01). Although the chronically infected lungs were more sensitive to NOS inhibition, further evidence suggested that the increased iNOS expression was not associated with enhanced iNOS activity. Selective inhibitors of iNOS did not produce an increase in vascular resistance similar to that produced by nonselective inhibitors. Accumulation of nitrate/nitrite in the perfusate of isolated lungs was unchanged by chronic infection. Thus although iNOS expression was increased in chronic pulmonary infection, iNOS activity in the intact lung was not. Nonetheless, endogenous NO production was essential to maintain normal vascular resistance in these lungs. pulmonary vascular resistance; hypoxia; Pseudomonas aeruginosa ; aminoguanidine; nitrate; nitrite