MGSO4 RELAXES PORCINE AIRWAY SMOOTH-MUSCLE BY REDUCING CA2+ ENTRY

Magnesium sulfate (MgSO4) is used clinically, but its mechanism of act ion is unknown. To determine whether MgSO4 relaxes airway smooth muscl e and to investigate the pathways involved, we compared effects of MgS O4 in porcine tracheal and bronchial muscles contracted with either ca rbachol or KCl and measured the effects of MgSO4 on the concentration of intracellular free calcium ([Ca2+](i)). Lungs were dissected after anesthesia and exsanguination. Tracheal strips and bronchial rings wer e suspended in tissue baths for measurement of isometric tension in th e presence of different concentrations of MgSO4. In separate experimen ts, tracheal smooth muscle tension and [Ca2+](i) were measured simulta neously, using the fluorescent dye fura 2. MgSO4 (1.2, 2.2, 9.2 mM) pr oduced a concentration-dependent rightward shift of contraction dose-r esponse curves to KCl but not to carbachol. MgSO4 relaxed trachealis m uscles precontracted with KCl or carbachol and simultaneously decrease d [Ca2+](i). These findings indicate that MgSO4 directly relaxes airwa y smooth muscle and that the mechanism involves a decrease in [Ca2+](i ). Because initiation and maintenance of contraction during KCl stimul ation and maintenance of contraction during carbachol stimulation requ ire Ca2+ entry through voltage-dependent calcium channels, MgSO4-induc ed relaxation may involve a decrease in Ca2+ entry via these channels.