title: Effect of leukotriene and thromboxane antagonist on propranolol-induced bronchoconstriction.
abstract: beta-adrenoreceptor blockers such as propranolol provoke bronchoconstriction only in asthmatic patients. Although cysteinyl leukotrienes (cLTs) and thromboxane A2 (TXA2) have been proposed to be involved in the pathophysiology of asthma, the role of these lipid mediators in propranolol-induced bronchoconstriction (PIB) has not been evaluated in asthmatics. This study was conducted to elucidate it. Nine patients with stable asthma, in whom a 20% or more decrease in FEV(1) occurred by inhalation of 20 mg/ml or less propranolol, participated in this study. A cLT antagonist, pranlukast (225 mg twice a day), a TXA2 antagonist, seratrodast (80 mg once a day), and placebo were orally given for 2 wk in a randomized and double-blinded manner. The provocative concentration of propranolol causing a 20% fall in FEV(1) (PC(20)) was determined on the last day of each 2-wk treatment. Pranlukast, but not seratrodast, tented to increase FEV(1) compared with placebo (2.14 +/- 0.29 versus 1.99 +/- 0.34 L, p = 0.0543). Pranlukast or seratrodast did not affect the PC(20) in comparison with placebo. We conclude that cLTs or TXA2 are not involved in PIB of asthmatics.
authors.affiliation: The Third Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fujimura
authors.forename: M
authors.initials: M
authors.lastname: Abo
authors.forename: Y
authors.initials: Y
authors.lastname: Kamio
authors.forename: S
authors.initials: S
authors.lastname: Myou
authors.forename: Y
authors.initials: Y
authors.lastname: Ishiura
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001249:Asthma / Q000503:physiopathology*; D016227:Benzoquinones / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D002867:Chromones / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D016227:Benzoquinones; D002867:Chromones; D006538:Heptanoic Acids; D020024:Leukotriene Antagonists; C060230:seratrodast; D013928:Thromboxane A2; D011433:Propranolol; C047681:pranlukast