In vivo bronchodilator activity of nifedipine in the guinea pig.
We administered histamine subcutaneously to anesthetized guinea pigs to induce prolonged bronchoconstriction and then tested the effect of intravenously administered nifedipine on pulmonary resistance (RL) and dynamic compliance (Cdyn). One mg of subcutaneously administered histamine caused RL to increase by an average of more than 250% and Cdyn to fall on average to 26% of baseline; mean RL remained more than twice baseline, and mean Cdyn remained less than half baseline for 80 min. Intravenously administered nifedipine 3 micrograms/kg and ethanol (diluent) administered 25 min after histamine had no effect on RL but caused a slightly greater fall in Cdyn than in the control animals treated with histamine alone. Nifedipine 30 micrograms/kg, however, exhibited significant bronchodilator activity: 35 min after nifedipine 30 micrograms/kg, RL decreased on average to 41 +/- 17% above baseline (p less than 0.02), and Cdyn increased to 49 +/- 5% below baseline (p less than 0.0001). By comparison, isoproterenol (0.3 to 3.0 micrograms/kg) caused bronchodilation of more rapid onset (within 1 min) and shorter duration of action (approximately 10 min). Thus, we were able to demonstrate bronchodilator activity of nifedipine in vivo, as had been predicted by in vitro studies of guinea pig and human tracheal strips. These results would appear to justify continued exploration of the potential role for calcium channel blockers in the treatment of obstructive lung disease.
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D001993:Bronchodilator Agents; D003251:Constriction, Pathologic / Q000139:chemically induced / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D000431:Ethanol / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000627:therapeutic use*; D013997:Time Factors
D001993:Bronchodilator Agents; D000431:Ethanol; D006632:Histamine; D009543:Nifedipine; D007545:Isoproterenol