Physiologic and molecular characterization of the role of nitric oxide in hemorrhagic shock: evidence that type II nitric oxide synthase does not regulate vascular decompensation

• Published in: Shock (Augusta, Ga.) Ga.), 1997-03, Vol.7 (3), p.157-163
• Main Authors: Kelly, E, Shah, N S, Morgan, N N, Watkins, S C, Peitzman, A B, Billiar, T R
• Format: Article
• Language: English
• Subjects: Animals; Aorta - anatomy & histology; Aorta - chemistry; Blotting, Northern; Capillary Permeability - physiology; Cyclic GMP - blood; Cyclic GMP - metabolism; Enzyme Inhibitors - pharmacology; Hemoglobins - physiology; Immunohistochemistry; Liver - anatomy & histology; Liver - chemistry; Lung - anatomy & histology; Lung - chemistry; Macrophages - chemistry; Macrophages - cytology; Male; Nitrate Reductases - blood; Nitrate Reductases - metabolism; Nitric Oxide - physiology; Nitric Oxide Synthase - physiology; Nitrite Reductases - blood; Nitrite Reductases - metabolism; omega-N-Methylarginine - pharmacology; Rats; Rats, Sprague-Dawley; Shock, Hemorrhagic - blood; Shock, Hemorrhagic - enzymology; Shock, Hemorrhagic - physiopathology; Vasoconstriction - physiology
• ISSN: 1073-2322
• DOI: 10.1097/00024382-199703000-00001

To determine the role of nitric oxide (NO) in decompensated and irreversible hemorrhagic shock, rats were subjected to hemorrhagic shock (HS) for 3 or 5 h. Lung, liver, and plasma samples were studied for evidence of NO formation using Northern analysis and immunohistochemistry for Type II NOS, as well as measurement of plasma nitrite/nitrate, cyclic GMP, and nitrosylated hemoglobin levels. Comparisons were made with similarly instrumented time-matched sham rats. Type II NOS mRNA and protein were detectable in lung and liver only in the irreversible phase of HS (5 h). A large accumulation of nitrosylated hemoglobin and nitrite/nitrate appeared in the irreversible phase. Significant accumulation of cyclic GMP or nitrite/nitrate was not detectable in the decompensation phase. Despite the hemodynamic decompensation at 3 h of HS, Type II NOS mRNA and protein expression, as well as NO metabolites were not elevated. To assess whether NO plays a physiologically significant role in decompensation, rats in the decompensation phase and sham animals were subjected to nonspecific NOS inhibition. Both groups displayed a similar magnitude and duration of blood pressure elevation. Hemodynamic decompensation in HS is not mediated by Type II NOS induction. NO production increases only after prolonged HS; significant NO production is observed only in severe, irreversible HS.