The beta(2)-agonist salbutamol inhibits bronchoconstriction and leukotriene D(4) synthesis after dry gas hyperpnea in the guinea-pig.
Isocapnic dry gas hyperpnea-induced bronchoconstriction (HIB) in the guinea-pig is mediated by both tachykinin release from airway sensory nerve C-type fiber terminals and secondary synthesis of cysteinyl-leukotrienes, in particular LTD(4). Beta (beta)(2)-agonists are potent bronchodilators but potentially could also inhibit the airway response to hyperpnea challenge via effects on the release of LTD(4)from airway cells in vivo. The purpose of this study was to test the hypothesis that beta(2)agonists attenuate HIB in guinea-pigs, in part, by reduction in LTD(4)release in vivo. Twenty-six guinea-pigs (400-550 g) were anesthetized with xylazine (7 mg/kg) and pentobarbital (65 mg/kg), tracheotomized and mechanically ventilated with a small animal ventilator using a tidal volume of 3 ml and a breathing frequency of 60 breaths/min. Dry gas (95%O(2)/5%CO(2)) with a 4 ml tidal volume and a breathing frequency of 150/min was used for hyperpnea challenge. Challenge with isocapnic dry gas triggered a significant increase in pulmonary resistance (0.3 +/- 0.02 vs. 0.57 +/- 0.06 cmH(2)O/ml per s; P=0. 017; n=13) and excretion of LTD(4)in the bile (baseline: 2.43 vs. HIB: 4.66 pmol/h; P=0.04). Salbutamol pretreatment completely blocked the airway response to the challenge (0.3+/-0.02 vs. 0.3+/-0. 05 cmH(2)O/ml per s; n=13) and reduced the biliary excretion of LTD(4)(baseline: 2.42 pmol/h; vs. HIB: 2.40 pmol/h). We conclude that salbutamol inhibited the airway responses to dry gas hyperpnea challenge and LTD(4)synthesis by the airway cells.
Yang
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Meakins-Christie Laboratories, McGill University, Montreal, Quebec, H2X 2P2, Canada.
Ho
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Xu
L J
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Powell
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Martin
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JG
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D001659:Biliary Tract / Q000378:metabolism; D016084:Bronchoconstriction / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D006168:Guinea Pigs; D017998:Leukotriene D4 / Q000096:biosynthesis*; D008168:Lung / Q000378:metabolism; D008297:Male; D011863:Radioimmunoassay; D012121:Respiration, Artificial; D015656:Respiratory Mechanics / Q000502:physiology*
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D017998:Leukotriene D4; D000420:Albuterol