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NOS1‐derived nitric oxide as a signaling effector for the initiation of systemic inflammatory reaction in sepsis models
Author(s) -
Duma Danielle,
Fernandes Daniel,
Assreuy Jamil
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a441-d
Subject(s) - nitric oxide , sepsis , lipopolysaccharide , septic shock , inflammation , nitric oxide synthase , systemic inflammation , nitrite , medicine , pharmacology , hemodynamics , tumor necrosis factor alpha , immunology , chemistry , anesthesia , nitrate , organic chemistry
Nitric oxide (NO) has been recognized as one of the most versatile players in the immune system. The high production of NO by indulcible NO synthase (NOS2) is responsible for sepsis‐induced hypotension. We investigated the role of NOS1‐derived NO in the development of systemic inflammatory reaction in rats induced by lipopolysaccharide (LPS, 10mg/Kg, i.p.) injection and/or cecal ligation and puncture (CLP) surgery. Injection of the selective NOS1 inhibitor 7‐nitroindazole (7NI, 1.2 μmol/Kg, i.p.) before LPS prevented both endotoxin‐induced acute hypotension and increase in nitrite + nitrate skeletal muscle content. Pre‐treatment of rats with 7NI prevented inflammatory and hemodynamic changes that appear hours after the inflammatory stimuli, LPS injection and CLP surgery. Pre‐treatment with 7NI also increased the survival time of endotoxic/septic animals. However, 7NI failed to modify the inflammatory/hemodynamic changes if administered after the inflammatory stimuli. In addition, administration of a NO donor (SNAP 1.4 μmol/Kg, i.p.) to 7NI‐treated animals abolished the protective effect of the NOS inhibitor in endotoxic/septic rats. Collectively our data suggests that a rapid “pulse” of NO released from NOS1 soon after the onset of an inflammatory reaction is important as a signaling mechanism for the subsequent development of systemic inflammation and hemodynamic changes of endotoxic/septic shock