The effects of L-NG-nitroarginine in a zymosan-induced multiple organ dysfunction syndrome model.
BACKGROUND
The aim of this study was to investigate the role of nitric oxide in mesenteric ischemia, organ injury and survival in zymosan-induced multiple organ dysfunction syndrome (MODS) by using the nonselective nitric oxide synthase inhibitor L-N(G)-nitroarginine (L-NNA).


METHODS
Swiss albino mice (20-40 g) were used in the study. The animals were randomly divided into four groups. The first group was treated intraperitoneally with saline and served as the sham group for L-NNA. The second group was treated with zymosan (500 mg/kg). The mice in the third and fourth group received L-NNA (20 mg/kg), 1 and 6 h after saline or zymosan administration. Six hours after the administration of zymosan, animals were used for mesenteric arterial blood flow (MABF) measurements and then sacrificed for biochemical and histopathological analyses at the 18th hour.


RESULTS
In zymosan-treated animals, MABF was significantly lower than that of solvent saline-treated controls (controls: 4.7 +/- 0.8 ml.min(-1); zymosan: 1.7 +/- 0.7 ml.min(-1), p < 0.05). L-NNA did not prevent zymosan-induced MABF decrease (controls: 4.5 +/- 0.8 ml.min(-1); zymosan: 2.5 +/- 1.4 ml.min(-1), p <0.05). Also treatment with L-NNA has no beneficial effect on survival and organ injury in zymosan-induced MODS.


CONCLUSIONS
In this study, inhibition of both inducible and constitutive nitric oxide synthase by L-NNA did not abolish the harmful effects of zymosan. L-NNA remains an agent without any therapeutic potential in this acute experimental model of MODS.
Ozel
H
H
Department of General Surgery, Ankara Numune Education and Research Hospital, Ankara, Turkey.
Yuksel
B C
BC
Berkem
H
H
Avsar
F M
FM
Guler
G
G
Iskit
A B
AB
Guc
M O
MO
Hengirmen
S
S
D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051379:Mice; D009102:Multiple Organ Failure / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000503:physiopathology; D013152:Splanchnic Circulation / Q000187:drug effects; D015054:Zymosan / Q000633:toxicity
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D015054:Zymosan; D019001:Nitric Oxide Synthase