title: 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.
abstract: 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.
authors.affiliation: Department of Surgery, University of Pittsburgh, Pennsylvania 15261, USA.
authors.forename: E
authors.initials: E
authors.lastname: Kelly
authors.forename: N S
authors.initials: NS
authors.lastname: Shah
authors.forename: N N
authors.initials: NN
authors.lastname: Morgan
authors.forename: S C
authors.initials: SC
authors.lastname: Watkins
authors.forename: A B
authors.initials: AB
authors.lastname: Peitzman
authors.forename: T R
authors.initials: TR
authors.lastname: Billiar
mesh_terms: D000818:Animals; D001011:Aorta / Q000033:anatomy & histology / Q000737:chemistry; D015152:Blotting, Northern; D002199:Capillary Permeability / Q000502:physiology; D006152:Cyclic GMP / Q000097:blood / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006454:Hemoglobins / Q000502:physiology; D007150:Immunohistochemistry; D008099:Liver / Q000033:anatomy & histology / Q000737:chemistry; D008168:Lung / Q000033:anatomy & histology / Q000737:chemistry; D008264:Macrophages / Q000737:chemistry / Q000166:cytology; D008297:Male; D009565:Nitrate Reductases / Q000097:blood / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology; D009572:Nitrite Reductases / Q000097:blood / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000097:blood* / Q000201:enzymology / Q000503:physiopathology; D014661:Vasoconstriction / Q000502:physiology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D006454:Hemoglobins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D009565:Nitrate Reductases; D009572:Nitrite Reductases; D006152:Cyclic GMP