Relaxant effects of amrinone upon pulmonary smooth muscle

Amrinone, a cardiac positive inotropic agent, inhibited histamine-induced bronchoconstriction in a dose-related manner in dogs when administered intra-duodenally at doses ranging from 0.3 to 10 mg/kg. This bronchodilatory property of amrinone in vivo was confirmed in vitro: amrinone relaxed carbachol-induced contractions and it inhibited Ba2+- or histamine-induced contractions of guinea pig tracheas. When amrinone was examined for its inhibition of histamine contractions under modified Ca2+ availability, the EC25 and EC75 of amrinone were 76 and 8 times smaller, respectively, under conditions of intracellular rather than normal Ca2+ availability. The corresponding decreases for verapamil were 12,414 and 33 times. No meaningful changes in the potencies of amrinone or verapamil were seen when normal Ca2+ availability was changed to extracellular Ca2+ availability. These data suggest that verapamil, and partially amrinone, inhibit histamine-induced tracheal contractions by reducing the bioavailability of intracellular Ca2+.