The effects of selective nitric oxide synthase blocker on survival, mesenteric blood flow and multiple organ failure induced by zymosan.
BACKGROUND
Circulatory failure in multiple organ dysfunction syndromes (MODS) is characterized with systemic vasodilation, diminished blood flow to various vascular beds. The aim of this study was to investigate the effects of selective inhibition of nitric oxide on the mesenteric arterial blood flow (MABF), survival and organ injury of the liver, kidney, lung and spleen in zymosan-induced MODS.


METHODS
Forty Swiss albino mice (20-40 g), 7 to 9 weeks old, were obtained. Animals were randomly divided into four groups. The first group were treated intraperitoneally (i.p) with vehicle (saline) and served as a sham group for aminoguanidine (AG) (n=10). The second group was treated with zymosan (500 mg/kg, suspended in saline solution, i.p). The mice in the third and fourth group received AG (15 mg/kg) 1 h and 6 h after zymosan or saline administration, respectively. Eighteen hours after the administration of zymosan, animals were assessed for MODS described subsequently. The signals from the flowmeter were also recorded on mesenteric arterial blood flow values.


RESULTS
In zymosan-treated animals, the MABF was significantly lower than that of solvent (saline)-treated controls (ml min(-1), controls: 4.6 +/- 0.6; zymosan: 1.6 +/- 0.9, P <0.05). When animals were treated with AG, there were no significant differences in MABF values between AG group and solvent (saline)-treated control group. However AG prevented zymosan-induced mesenteric MABF decrease. Treatment with aminoguanidine also decreased mortality.


CONCLUSIONS
AG is capable of inhibiting both the induction and the activity of the already iNOS; it remains a potential therapeutic agent in patients with MODS.
Tanriverdi
Pinar
P
Department of General Surgery, Ankara Numune Education and Research Hospital, Ankara, Turkey.
Yuksel
Bulent C
BC
Rasa
Kemal
K
Guler
Gulnur
G
Iskit
Alper B
AB
Guc
M Oguz
MO
Korkmaz
Atilla
A
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D051379:Mice; D009102:Multiple Organ Failure / Q000139:chemically induced / Q000188:drug therapy*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D013152:Splanchnic Circulation / Q000187:drug effects*; D013154:Spleen / Q000187:drug effects; D016019:Survival Analysis; D015054:Zymosan / Q000009:adverse effects; D047071:beta-Glucans / Q000009:adverse effects
D004791:Enzyme Inhibitors; D006146:Guanidines; D047071:beta-Glucans; D015054:Zymosan; D019001:Nitric Oxide Synthase; C004479:pimagedine