- Meeting abstract
Endotoxin-induced pulmonary hyporesponsiveness to inhaled nitric oxide is improved by nitric oxide synthase 2 inhibition
Critical Care volume 4, Article number: P52 (2000)
In isolated-perfused lungs of endotoxin-challenged rats, inhibition of nitric oxide synthase 2 (NOS2) by aminoguanidine (AG) improved responsiveness to inhaled nitric oxide (NO) . In dogs treated with lipopolysaccharide (LPS), S-methylisothiourea (SMT) and AG prevented worsening of hemodynamics and gas exchange . In this study, inhibition of NOS2 by SMT and AG modulates responsiveness to inhaled NO in lungs of endotoxin (LPS)-challenged rats in a dose-dependent manner.
Sprague-Dawley rats (400-450 gm BW) were injected i.p. with 0.5 mg/kg E. coli 0111:B4 LPS (n=42) or were controls (n=9). Four hours later, LPS-treated rats were injected i.p. with 3, 10, and 30 mg/kg AG or 0.01, 0.1, 1 and 10 mg/kg SMT. 18 h later, lungs were isolated-perfused in situ using Hank's solution. Pulmonary artery pressure (PAP) was elevated by 6-8 mmHg using the thromboxane analogue U46619. Decrease of PAP in response to inhaled NO (0.4, 4, and 40 ppm NO in random order) was measured. Serum and lung perfusate nitrate/nitrite levels were measured with the Griess-reaction.
AG is more effective in improving NO responsiveness than SMT. Responsiveness to inhaled NO appears to be dependent on the degree of NOS2 inhibition in lungs of LPS-challenged rats, because improvement of NO responsiveness correlated with nitrate/nitrite levels in serum and lung perfusate.
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Bopp, C., Holzmann, A., Schmidt, H. et al. Endotoxin-induced pulmonary hyporesponsiveness to inhaled nitric oxide is improved by nitric oxide synthase 2 inhibition. Crit Care 4 (Suppl 1), P52 (2000). https://doi.org/10.1186/cc772