Effect of beta 2-adrenoceptor agonists against platelet-activating factor-induced airway microvascular leakage and bronchoconstriction in the guinea pig.
We have investigated the effect of inhaled formoterol (0.75 mg/ml, 60 breaths) and salbutamol (25 mg/ml, 60 breaths) against airway microvascular leakage and bronchoconstriction induced by inhaled platelet-activating factor (PAF) and histamine in anaesthetized guinea pigs. Lung resistance (RL) was measured for 6 min after challenge, followed by measurement of extravasation of Evans blue dye into airway tissues, used as an index of airway microvascular leakage. PAF (0.1, 0.4 and 1 mM; 30 breaths) caused a significant increase in RL and extravasation of dye, but the responses were smaller than those induced by histamine (5 mM, 30 breaths). Both formoterol and salbutamol caused a small but significant inhibition of extravasation in the distal intrapulmonary airways induced by PAF (0.1 and 0.4 mM for formoterol and 0.1 mM for salbutamol), and only formoterol reduced the increase in RL induced by 1 mM PAF. These drugs also inhibited both airway effects of histamine to a higher degree. In conclusion, formoterol and salbutamol can partly inhibit airway microvascular leakage and bronchoconstriction induced by inhaled PAF and histamine. The inhibitory potency of beta 2-adrenoceptor agonists may be dependent on the inflammatory mediator inducing the airway effects.
Sakamoto
T
T
Department of Thoracic Medicine, National Heart and Lung Institute, London, UK.
Barnes
P J
PJ
Chung
K F
KF
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000420:Albuterol / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D000068759:Formoterol Fumarate; D006168:Guinea Pigs; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D010972:Platelet Activating Factor; D018343:Receptors, Adrenergic, beta-2; D006632:Histamine; D000420:Albuterol; D000068759:Formoterol Fumarate