Selective inhibition of guanylate cyclase prevents impairment of hypoxic pulmonary vasoconstriction in endotoxemic mice

• Autorzy: Spohr F. , Busch C.J. , Teschendorf P. , Weimann J.
• Języki publikacji: EN

Abstrakty

EN

Nitric oxide (NO) may cause sepsis-induced impairment of hypoxic pulmonary vasoconstriction (HPV). Although NO exerts many of its actions by activating soluble guanylate cyclase (sGC), there are several cGC-independent mechanisms that may lead to NO-induced vasodilation during endotoxemia. We investigated the role of sGC for the regulation of HPV during lipopolysaccharide (LPS) induced endotoxemia using 1H-(1,2,4)oxadiazole(4,3-)quinoxaline-1-one (ODQ), a specific inhibitor of sGC, in isolated, perfused, and ventilated mouse lungs. Without ODQ, lungs from LPS-challenged mice constricted significantly less in response to hypoxia as compared to lungs from mice not treated with LPS (26 ± 27% vs. 134 ± 37%, respectively, p < 0.05). 20 mg/kg ODQ, but not 2 mg/kg or 10 mg/kg, restored the blunted HPV response in LPS-challenged mice as compared to mice not challenged with LPS (80±14 % vs. 98±21 %). ODQ had no effect on baseline perfusion pressures under normoxic conditions. Analysis of pulmonary vascular P-Q relationships suggested that the restoration of pulmonary vascular response to hypoxia by ODQ is associated with a restoration of pulmonary vascular properties during normoxia. Our data show in a murine model that specific inhibition of sGC may be a new approach to restore HPV during endotoxemia.

Słowa kluczowe

EN

hypoxic pulmonary vasoconstriction; selective inhibition; endotoxemia; nitric oxide; mouse; guanylate cyclase; lung; mice; endotoxaemia zob.endotoxemia; vasoconstriction

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2009
• Tom: 60
• Numer: 2
• Opis fizyczny: p.107-112,fig.,ref.

Twórcy

autor

Spohr F.

• University of Cologne, Cologne, Germany

autor

Busch C.J.

autor

Teschendorf P.

autor

Weimann J.