Role of cysteinyl-leukotrienes and histamine in mediating intrinsic tone in isolated human bronchi.
The intrinsic isometric tone of human isolated intralobar bronchi was evaluated in vitro. Human bronchi (inner diameter, 3 to 12 mm) were obtained from patients undergoing lung resection and from organ donors. The organ donor tissue was studied approximately 24 h after resection, during which time it was shipped to the laboratory in RPMI 1640 medium at 4 degrees C. The bronchi obtained from patients with cancer was placed in the same medium and studied within 4 h of resection. All tissues were suspended in 10-ml organ baths containing oxygenated Krebs' solution at 37 degrees C, at an initial load of 2 g. Tissues were washed every 15 min until they exhibited a stable tension (usually 60 min). Under these conditions the amount of active tension in the bronchi studied on the day of resection averaged 65 +/- 9% of the maximal response to BaCl2 (30 mM), whereas after overnight incubation it averaged 31 +/- 6%. Neither indomethacin nor atropine influenced the intrinsic tone in these tissues. By contrast, the LTD4 antagonists SKF 104353 and ICI 198615 and the histamine H-1 antagonists pyrilamine and chlorpheniramine effectively relaxed the bronchi. The 5' lipoxygenase inhibitor zileuton also produced a small fall in tension. Studies in which pyrilamine was combined with the leukotriene receptor antagonists indicated an additive effect. These results indicate that human bronchial smooth muscle exhibits a high degree of intrinsic tone, averaging more than 50% of available tone in fresh tissues studied in vitro under isometric conditions. The results suggest that this tone is due to the continual production and release of histamine and cysteinyl-leukotrienes.
Ellis
J L
JL
Division of Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224.
Undem
B J
BJ
D001980:Bronchi / Q000187:drug effects* / Q000502:physiology*; D002744:Chlorpheniramine / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D007552:Isotonic Solutions; D017998:Leukotriene D4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009129:Muscle Tonus / Q000187:drug effects* / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011738:Pyrilamine / Q000494:pharmacology; D013189:SRS-A / Q000037:antagonists & inhibitors
D003998:Dicarboxylic Acids; D007191:Indazoles; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D016859:Lipoxygenase Inhibitors; D013189:SRS-A; C054217:ICI 198615; D002744:Chlorpheniramine; D017998:Leukotriene D4; D006632:Histamine; D011738:Pyrilamine; C052393:pobilukast; C063449:zileuton; D006918:Hydroxyurea