Hyporesponsiveness to inhaled nitric oxide in isolated, perfused lungs from endotoxin-challenged rats.

摘要: Inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves oxygenation in patients with the adult respiratory distress syndrome (ARDS). Approximately 30% of ARDS fail to respond iNO. Because sepsis often accompanies a decreased response iNO, we investigated NO responsiveness isolated, perfused lungs from rats exposed lipopolysaccharide (LPS). Eighteen hours after intraperitoneal injection 0.5 mg/kg LPS, rat were perfused, preconstricted U-46619. Ventilation 0.4, 4, 40 parts per million by volume vasodilated LPS-pretreated 75, 47, 42% less than control (P < 0.01 value differs at each concentration). The diminished vasodilatory iNO was associated NO-stimulated guanosine 3',5'-cyclic monophosphate (cGMP) release into perfusate. Soluble guanylate cyclase activity did not differ lung extracts rats. LPS increased cGMP-phosphodiesterase (PDE) 40%. PDE-sensitive cGMP analogue 8-bromoguanosine In contrast, PDE-insensitive 8-para-chlorophenylthioguanosine equally both groups. After challenge, vasculature becomes hyporesponsive Hyporesponsiveness appears partly attributable cGMP-PDE activity.