Methylprednisolone Attenuates Airway and Vascular Responses Induced by Reactive Oxygen Species in Isolated, Plasma-Perfused Rat Lungs

Abstract

The effects of methylprednisolone (MP) on the acute airway and pulmonary vascular responses induced by reactive oxygen species (ROS) were investigated in isolated, plasma-perfused rat lungs. ROS were generated by adding xanthine oxidase and hypoxan-thine to the perfusate. MP was administered in 3 different ways: 1. Added to the perfusate (1 mg*ml^-1) 5 min prior to xanthine oxidase and hypoxanthine, 2. Given as intraperitoneal injections (40 mg*kg^-1) to lung donor rats 12 and 2 hours prior to the experiments, or 3. Combining 1 and 2. The lungs were perfused at constant volume inflow (15 ml*min^-1). Pulmonary arterial pressure and transpulmonary pressure were followed for 30 min after addition of xanthine oxidase and hypoxanthine. ROS induced a powerful, acute broncho- and vasoconstriction, which was inhibited by addition of MP to the perfusate. Pretreatment with MP also inhibited the vascular and airway responses. Adding MP to the perfusate of pretreated lungs further reduced the ROS-induced smooth muscle constriction. In conclusion, MP inhibits vasoconstriction and bronchocon-striction induced by ROS in isolated rat lungs.

Key Words:

• Adult respiratory distress syndrome
• bronchocon-striction
• corticosteroids
• free radicals
• lung injury
• pulmonary vasoconstriction.