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+.
D000403:Airway Resistance / Q000187:drug effects*; D000628:Aminophylline / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology*; D000676:Amrinone; D000818:Animals; D001464:Barium / Q000037:antagonists & inhibitors; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D004347:Drug Interactions; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D000631:Aminopyridines; D006633:Histamine Antagonists; D001464:Barium; D000628:Aminophylline; D002217:Carbachol; D014700:Verapamil; D000676:Amrinone; D002118:Calcium