Effects of Ca2+ antagonist, nicardipine, on experimental asthma with special reference to slow reacting substance of anaphylaxis.
Slow reacting substance of anaphylaxis (SRS-A) is an important chemical mediator of bronchial asthma. Leukotriene C4 is a component of SRS-A and is synthesized from arachidonic acid. Its synthesizing and releasing processes are found to be Ca2+-dependent. We developed an in vivo inhalation asthma model, mainly mediated by SRS-A, and elucidated the relationship between a Ca2+-antagonist, nicardipine, and SRS-A. In the asthmatic model, mediated by endogenous SRS-A induced by antigen inhalation, continuous intravenous infusion of nicardipine 7 micrograms/kg/min depressed the open airway pressure by about 60% compared with the saline-treated group. Inhibition of mean pulmonary resistance (RL) was about 50% and that of the inverted value of dynamic compliance (1/Cdyn) about 36%. However, the same concentration of nicardipine did not significantly effect the airway response in the asthmatic model induced by the inhalation of leukotriene C4. These results suggest that nicardipine, at the concentration used in the present study. did not block the direct effect of SRS-A on the smooth muscle, but blocked the Ca2+ influx required for the synthesis of SRS-A and its release.
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D006168:Guinea Pigs; D008297:Male; D009529:Nicardipine; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010047:Ovalbumin / Q000276:immunology; D013189:SRS-A / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology
D000941:Antigens; D002121:Calcium Channel Blockers; D013189:SRS-A; D010047:Ovalbumin; D009529:Nicardipine; D009543:Nifedipine