Nifedipine decreases sensitivity and reactivity to methacholine in mild asthmatics

The protective effect of the calcium antagonist nifedipine (20 mg sublingually) on methacholine-induced bronchospasms was investigated in 14 mild asthmatics, 8 extrinsic and 6 intrinsic, in stable situations and with FEV1 greater than or equal to 80% of the one predicted. On separate days cumulative dose-response curves to methacholine were constructed, basal and 20 min after nifedipine administration; on both occasions basal FEV1 varied less than 5%. The sensitivity threshold (PD20) and reactivity (slope of the curve) were obtained. The shape of the curves analyzed from the PD20 point on, was linear (r2 = 0.99). There was a strong hyperbolic correlation between sensitivity and reactivity (r2 = 0.89). Nifedipine did not modify basal FEV1. After nifedipine, the sensitivity to methacholine decreased from 36.7 +/- 10.5 to 61.0 +/- 15.8 SEM (p less than 0.01) and likewise the reactivity from 2.2 +/- 0.7 to 1.1 +/- 0.5 SEM (p less than 0.02). Protection was greater when the basal sensitivity was higher (r = 0.59, p less than 0.05) but no such correlation was found for reactivity. Protection is explained by the blocking effect of nifedipine of calcium flux through voltage-dependent channels, provided that muscarinic agonists, at low doses, act preferentially through electromechanical coupling. These results indicate that a distinction between sensitivity and reactivity does not provide more information than each separate parameter.