Expression of dihydropyridine resistance differs in porcine bronchial and tracheal smooth muscle.
Voltage-dependent and receptor-operated Ca2+ entry mechanisms have been demonstrated in airway smooth muscle, but their relative importance for maintenance of contraction is unknown. Blockade of voltage-dependent Ca2+ channels (VDC) has produced inconsistent relaxation. We postulated regional variations in Ca2+ handling by airway smooth muscle cells and compared the efficacy of dihydropyridine VDC blockers in tracheas and bronchi. Porcine tracheal smooth muscle strips and bronchial rings were mounted in tissue baths filled with physiological solutions and isometric tension was measured. Tissues were precontracted with carbachol or KCl, and relaxation dose-response curves to nifedipine, Mn2+, or Cd2+ were obtained. Relaxation responses to nifedipine were significantly different in carbachol-contracted tracheas and bronchi. Whereas carbachol-contracted tracheal muscle completely relaxed with 10(-6) M nifedipine, bronchial smooth muscle relaxed < 50%. In contrast, KCl-contracted bronchial muscle was completely relaxed by nifedipine. The nonspecific Ca2+ channel blockers Mn2+ and Cd2+ produced similar relaxation responses in each tissue. Thus VDC are the predominant mechanism for Ca2+ entry in porcine tracheal smooth muscle, but a dihydropyridine-insensitive pathway is functionally important in carbachol-contracted porcine bronchi. Regional variation may account for apparent inconsistencies between previous studies.
Croxton
T L
TL
Department of Environmental Health Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Fleming
C
C
Hirshman
C A
CA
D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D002104:Cadmium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D008297:Male; D008345:Manganese / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D013552:Swine; D014132:Trachea / Q000187:drug effects*
D002104:Cadmium; D008345:Manganese; D011189:Potassium Chloride; D002217:Carbachol; D009543:Nifedipine