Abstract
The inducible isoform of nitric oxide synthase (iNOS) is expressed in various organs, including the lung, during systemic endotoxemia. Overproduction of nitric oxide (NO) by iNOS contributes significantly to the vascular failure and end-organ damage in endotoxemia. Using selective pharmacological inhibitors of iNOS, the purpose of this study was to define the role of iNOS in a rat model of endotoxin-induced pulmonary transvascular flux (TVF). Lung TVF was assessed by a method of Evans Blue permeability index (PI). Bacterial lipopolysaccharide (LPS) (15 mg/kg intraperitoneally [IP]) significantly increased pulmonary iNOS activity and serum levels of nitrite/nitrate (NO2/NO3). This was accompanied by a significant elevation of the PI 6 hours after injection. Selective iNOS inhibition with either S- methyl isothiourea (SMT; 5 mg/kg IP) or aminoguanidine (AG; 20 mg/kg IP), administered 2 hours after LPS injection, significantly prevented the increase in PI associated with LPS injection. Similarly, inhibition of the induction of iNOS with dexamethasone (10 mg/kg IP), given 3 hours before LPS, also inhibited the increase in PI. All three treatments significantly prevented the increase in both lung iNOS activity and serum NO2/NO3 associated with endotoxemia. In conclusion, the overproduction of NO generated by iNOS during systemic endotoxemia causes a vascular leak in the lung. Thus, it is speculated that selective inhibition of iNOS may be beneficial in preventing the development of acute respiratory failure in sepsis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1009-1015 |
| Number of pages | 7 |
| Journal | Journal of Pediatric Surgery |
| Volume | 31 |
| Issue number | 8 |
| State | Published - 1996 |
| Externally published | Yes |
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Keywords
- adult respiratory distress syndrome
- extravasation
- lung failure
- nitric oxide
- permeability index
- Sepsis
ASJC Scopus subject areas
- Surgery
Cite this
Selective inhibition of the inducible isoform of nitric oxide synthase prevents pulmonary transvascular flux during acute endotoxemia. / Arkovitz, M. S.; Wispe, J. R.; Garcia, V. F.; Szabo, Csaba; Arensman, R. M.
In: Journal of Pediatric Surgery, Vol. 31, No. 8, 1996, p. 1009-1015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Selective inhibition of the inducible isoform of nitric oxide synthase prevents pulmonary transvascular flux during acute endotoxemia
AU - Arkovitz, M. S.
AU - Wispe, J. R.
AU - Garcia, V. F.
AU - Szabo, Csaba
AU - Arensman, R. M.
PY - 1996
Y1 - 1996
N2 - The inducible isoform of nitric oxide synthase (iNOS) is expressed in various organs, including the lung, during systemic endotoxemia. Overproduction of nitric oxide (NO) by iNOS contributes significantly to the vascular failure and end-organ damage in endotoxemia. Using selective pharmacological inhibitors of iNOS, the purpose of this study was to define the role of iNOS in a rat model of endotoxin-induced pulmonary transvascular flux (TVF). Lung TVF was assessed by a method of Evans Blue permeability index (PI). Bacterial lipopolysaccharide (LPS) (15 mg/kg intraperitoneally [IP]) significantly increased pulmonary iNOS activity and serum levels of nitrite/nitrate (NO2/NO3). This was accompanied by a significant elevation of the PI 6 hours after injection. Selective iNOS inhibition with either S- methyl isothiourea (SMT; 5 mg/kg IP) or aminoguanidine (AG; 20 mg/kg IP), administered 2 hours after LPS injection, significantly prevented the increase in PI associated with LPS injection. Similarly, inhibition of the induction of iNOS with dexamethasone (10 mg/kg IP), given 3 hours before LPS, also inhibited the increase in PI. All three treatments significantly prevented the increase in both lung iNOS activity and serum NO2/NO3 associated with endotoxemia. In conclusion, the overproduction of NO generated by iNOS during systemic endotoxemia causes a vascular leak in the lung. Thus, it is speculated that selective inhibition of iNOS may be beneficial in preventing the development of acute respiratory failure in sepsis.
AB - The inducible isoform of nitric oxide synthase (iNOS) is expressed in various organs, including the lung, during systemic endotoxemia. Overproduction of nitric oxide (NO) by iNOS contributes significantly to the vascular failure and end-organ damage in endotoxemia. Using selective pharmacological inhibitors of iNOS, the purpose of this study was to define the role of iNOS in a rat model of endotoxin-induced pulmonary transvascular flux (TVF). Lung TVF was assessed by a method of Evans Blue permeability index (PI). Bacterial lipopolysaccharide (LPS) (15 mg/kg intraperitoneally [IP]) significantly increased pulmonary iNOS activity and serum levels of nitrite/nitrate (NO2/NO3). This was accompanied by a significant elevation of the PI 6 hours after injection. Selective iNOS inhibition with either S- methyl isothiourea (SMT; 5 mg/kg IP) or aminoguanidine (AG; 20 mg/kg IP), administered 2 hours after LPS injection, significantly prevented the increase in PI associated with LPS injection. Similarly, inhibition of the induction of iNOS with dexamethasone (10 mg/kg IP), given 3 hours before LPS, also inhibited the increase in PI. All three treatments significantly prevented the increase in both lung iNOS activity and serum NO2/NO3 associated with endotoxemia. In conclusion, the overproduction of NO generated by iNOS during systemic endotoxemia causes a vascular leak in the lung. Thus, it is speculated that selective inhibition of iNOS may be beneficial in preventing the development of acute respiratory failure in sepsis.
KW - adult respiratory distress syndrome
KW - extravasation
KW - lung failure
KW - nitric oxide
KW - permeability index
KW - Sepsis
UR - http://www.scopus.com/inward/record.url?scp=0029797733&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029797733&partnerID=8YFLogxK
M3 - Article
C2 - 8863222
AN - SCOPUS:0029797733
VL - 31
SP - 1009
EP - 1015
JO - Journal of Pediatric Surgery
JF - Journal of Pediatric Surgery
SN - 0022-3468
IS - 8
ER -