The effect of calcium antagonists on allergic pulmonary distress in actively sensitized rats.
The induction of allergic pulmonary distress (APD) in ovalbumin sensitive rats can be used as a model of human allergic asthma. In this model, control animals exhibit a rapid decrease in minute volume (Vm) when challenged with ovalbumin (OA) by aerosol (3% solution). The present study compared the effects of pretreatment with calcium antagonists on the induction of APD. By the aerosol route of administration, 5 min before OA, verapamil HCl (6% solution) significantly (P less than 0.05) dampened the allergic response during all 12 min monitored. At an equivalent concentration, diltiazem HCl significantly (P less than 0.05) inhibited the response during 6 of 12 min, whereas nifedipine failed to significantly (P greater than 0.05) alter the response to OA. Verapamil and nifedipine proved to be equally effective in a dose-dependent manner against OA-induced APD, however, when administered orally (-60 min, 5, 10 or 20 mg/kg). At doses of 10 mg/kg and higher, both calcium antagonists consistently inhibited (P less than 0.05) the response. Diltiazem was inactive when administered orally at a dose as high as 20 mg/kg. The present data suggest that the calcium antagonists verapamil, nifedipine and diltiazem, can attenuate APD and therefore might be clinically active agents in the treatment of allergic asthma.
Korach
E S
ES
Immunoinflammatory Diseases Research, Searle Research and Development, Division of G. D. Searle & Co. Skokie, Illinois.
Carnathan
G W
GW
Aspinall
R L
RL
D000284:Administration, Oral; D000336:Aerosols; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D009543:Nifedipine / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D000336:Aerosols; D002121:Calcium Channel Blockers; D010047:Ovalbumin; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine