Pharmacological characterization of effects of nifedipine on isolated guinea-pig and rat tracheal smooth muscle.
Nifedipine, a relatively new Ca2+-channel blocking agent, has recently been shown to be effective in the treatment of exercise-induced asthma; however, the pharmacological mechanism by which it blocks bronchospasm is little understood. We have investigated and characterized its effects on the reactivity of isolated guinea-pig and rat tracheal smooth muscle. Although it (10(-8)--10(-7)M) blocked the contraction of the rat tracheal muscle to KCl and CaCl2, nifedipine (10(-7)--10(-6)M) did not significantly inhibit histamine, methacholine or serotonin-induced muscle contractions in guinea-pigs and the methacholine contraction in rats. Nifedipine produced a potent relaxation on contracted tracheal muscle. The concentration required to produce 50% relaxation on 10(-5)M histamine-precontracted guinea-pig tracheal muscle was 8.31 +/- 3.12 X 10(-9)M, and the extent of the nifedipine-induced relaxation could be modified by the baseline and active contracted tension. Nifedipine was more potent in producing the relaxation in guinea-pig tracheal muscle than isoproterenol, theophylline or verapamil. However, the time required for 50% relaxation by 3 X 10(-5)M isoproterenol was significantly less than the time for the nifedipine (3 X 10(-5)M) or verapamil (10(-4)M) effect. In addition, the Hill number of the nifedipine-induced relaxation was different from the value of the isoproterenol or verapamil effect. Our results indicate that nifedipine exerts a potent dilatory effect directly on airway muscle, and suggest that such effect could be one of its pharmacological actions on relieving bronchospasm.
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D002121:Calcium Channel Blockers; D008688:Methacholine Compounds; D011725:Pyridines; D016210:Methacholine Chloride; D012701:Serotonin; D006632:Histamine; D009543:Nifedipine; D002122:Calcium Chloride