Inhibition of bronchoconstriction in the guinea pig by a calcium channel blocker, nifedipine.
We investigated the inhibitory effects of nifedipine, a calcium channel blocker, on airway smooth muscle constriction in the guinea pig. In vitro, nifedipine (0.003 to 3.0 microM) caused significant dose-dependent reversal of intrinsically existing tone in both tracheal spirals and parenchymal strips. Nifedipine also inhibited the constriction of tracheal spirals and parenchymal strips induced by two different agonists, histamine and carbachol. At a concentration of 3.0 microM, nifedipine increased by 48-fold the concentration of carbachol required to produce a 50% of maximal contraction of parenchymal strips, and by 5-fold the concentration of histamine. Increasing extracellular calcium ion concentration in the tissue baths significantly diminished the inhibitory action of nifedipine. In vivo, nifedipine (30 micrograms/kg body weight given intravenously) did not alter pulmonary resistance or dynamic compliance. It did, however, attenuate histamine-induced bronchoconstriction in 3 of 5 animals studied. In response to the maximal dose of histamine infused, mean pulmonary resistance rose 40 +/- 16% (SEM) after nifedipine versus 182 +/- 65% in the control animals (p less than 0.025) and mean dynamic compliance decreased 35 +/- 8% after nifedipine versus 58 +/- 6% in the control animals (p less than 0.01). Thus, this calcium channel blocker inhibits mediator-induced constriction of both central and peripheral airway contractile tissues, a finding of potential clinical applicability.
D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000503:physiopathology; D002217:Carbachol; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine; D066298:In Vitro Techniques; D008170:Lung Compliance / Q000187:drug effects; D008173:Lung Diseases, Obstructive / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology* / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects
D011725:Pyridines; D006632:Histamine; D002217:Carbachol; D009543:Nifedipine