title: Systemic biochemical effects of inhaled NO in rats: increased expressions of NOS III, nitrotyrosine-, and phosphotyrosine-immunoreactive proteins in liver and kidney tissues.
abstract: Inhaled nitric oxide (iNO) has been shown to reduce pulmonary hypertension associated with several disease states. The effects of iNO are thought to be restricted to the pulmonary vasculature because of its rapid inactivation by hemoglobin. Recent data have suggested, however, that iNO can form nitrosothiols, which can be carried throughout the circulation, thus increasing the half life and bioactivity on NO. Other studies have shown that iNO can affect intestinal ischemia and renal hemodynamics. In this study, rats were exposed to 49 +/- 4 ppm or 107 +/- 13 ppm NO for 4 h and the lung, spleen, liver, and kidney tissues were removed and measured for NOS II and NOS III protein, nitrotyrosine (NT), and phosphotyrosine (PT) immunoreactivity. Following 107 ppm iNO, increases in NOS III protein expression, NT, and PT were observed in the liver and kidney, but not in the lung or spleen. No such increases were noted after the lower dose of iNO. These results paralleled those shown for isobutyl nitrite that we reported earlier and indicated that iNO can cause changes in protein chemistry in organs and tissues beyond the lungs. Since iNO produced little systemic hemodynamic effects, it is unlikely that the observed biochemical alterations were derived secondarily from physiological changes.
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, Buffalo, New York 14260-1200, USA.
authors.forename: W B
authors.initials: WB
authors.lastname: Kielbasa
authors.forename: H L
authors.initials: HL
authors.lastname: Fung
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D019000:Phosphotyrosine / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism*
chemical_list: D011506:Proteins; D019000:Phosphotyrosine; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase