Accumulation of Nitrotyrosine Correlates with Endothelial NO Synthase in Pulmonary Resistance Arteries During Chronic Hypoxia in the Rat

• Published in: Pulmonary pharmacology & therapeutics Vol. 13; no. 4; pp. 157 - 165
• Main Authors: Demiryürek, AT, Karamsetty, MR, McPhaden, AR, Wadsworth, RM, Kane, KA, MacLean, MR
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-01-2000
• Subjects: Actins - metabolism; Animals; Arteries - metabolism; Arteries - pathology; Endothelium - metabolism; Hypertrophy, Right Ventricular - etiology; Hypoxia - complications; Hypoxia - metabolism; Immunohistochemistry; Lung - blood supply; Lung - metabolism; Lung - pathology; Nitric Oxide Synthase - metabolism; Nitrotyrosine, eNOS, Chronic hypoxia, Pulmonary artery, α-actin; Rats; Tyrosine - analogs & derivatives; Tyrosine - metabolism; Vascular Resistance; Nitrotyrosine, eNOS, Chronic hypoxia, Pulmonary artery, α-actin
• ISSN: 1094-5539; 1522-9629
• DOI: 10.1006/pupt.2000.0238

Nitrotyrosine and eNOS were detected immunocytochemically using specific antibodies in paraffin sections of lung from rats subjected to hypoxia for 2, 7, or 14 days. The staining intensity for eNOS was enhanced in the endothelium of both resistance and conduit pulmonary arteries at 2 days. Staining intensity for eNOS remained elevated at 7 and 14 days in conduit arteries, whereas it progressively increased further in resistance arteries. Nitrotyrosine staining was elevated to a similar degree in endothelium and adjacent vascular smooth muscle. In resistance pulmonary arteries, there was a progressive increase in nitrotyrosine, which matched the increase in eNOS. In conduit pulmonary arteries, nitrotyrosine increased only after 14 days of hypoxia. The results suggest that in chronic hypoxia the up-regulation of eNOS leads to the formation of peroxynitrite which has access to both endothelium and vascular smooth muscle.