The effects of diazoxide on total lung resistance in the anesthetized paralyzed guinea-pig

The initial effects of diazoxide on dynamic pulmonary compliance (CL) and flow resistance (RL) were measured in paralyzed, anesthetized guinea-pigs. Diazoxide (10, 20 or 40 mg/kg) caused a dose-related increase in RL and decrease in CL. The increase in RL could be selectively abolished by glossopharyngealotomy or decentralization, and by pretreatment with mepyramine (0.1 mg/kg) or disodium cromoglycate (10 mg/kg). Pretreatment with indomethacin (0.1 mg/kg) or acetylsalicylic acid (1 mg/kg) selectively eliminated the decreases in compliance observed after diazoxide. It is concluded that diazoxide initially constricts both large (RL) and small (CL) airways. The constriction of the large airways may involve a release of histamine, whereas the constriction of the small airways may be mediated by a prostaglandin or prostaglandin-like substance.