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.
Immunoinflammatory Diseases Research, Searle Research and Development, Division of G. D. Searle & Co. Skokie, Illinois.
E S
ES
Korach
G W
GW
Carnathan
R L
RL
Aspinall
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