Effect of nifedipine on constriction of human tracheal strips in vitro

1 Autopsy specimens of human trachealis muscle were used to investigate the effect of the calcium channel blocker, nifedipine, on airway smooth muscle constriction. With these tracheal strips, two consecutive cumulative concentration-effect curves to histamine (0.1-100 microM) obtained at a 60 min interval were highly reproducible. 2 We examined the effects of adding nifedipine (2.9 microM) to the incubation medium before the second histamine response. The concentration-effect relationships determined after nifedipine incubation were significantly different from control: the response to 100 microM histamine was reduced by approximately one-half (to 2.53 +/- 0.6 g; P less than 0.025), and the concentration of histamine causing 40% of the maximal control contraction (EC40) increased nearly ten fold (to 36.9 +/- 10.5 microM; P less than 0.02). 3 In two additional tracheal strips submaximally constricted with 10 microM histamine, nifedipine 2.9 microM caused complete relaxation to resting tension or below. 4 These results indicate a direct inhibitory effect of nifedipine on airway smooth muscle constriction and partial dependence of human trachealis muscle on calcium ion fluxes for initiation and maintenance of contraction. In addition, the results suggest a potential mechanism for the inhibitory effects of calcium channel blocking drugs in exercise-induced asthma.