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.
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.
Kelly
E
E
Department of Surgery, University of Pittsburgh, Pennsylvania 15261, USA.
Shah
N S
NS
Morgan
N N
NN
Watkins
S C
SC
Peitzman
A B
AB
Billiar
T R
TR
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
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