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Effect of beta 2-adrenoceptor agonists against platelet-activating factor-induced airway microvascular leakage and
T Sakamoto1, P J Barnes, K F Chung
1Department of Thoracic Medicine, National Heart and Lung Institute, London, UK.
Abstract:
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.
Insights
Formoterol and salbutamol partially inhibit airway microvascular leakage and bronchoconstriction caused by platelet-activating factor (PAF) and histamine. Their effectiveness may depend on the specific inflammatory mediator involved.
Area of Science:
- Pharmacology
- Respiratory Medicine
- Airway Inflammation
Background:
- Airway microvascular leakage and bronchoconstriction are key features of asthma.
- Platelet-activating factor (PAF) and histamine are potent mediators of airway inflammation.
Purpose of the Study:
- To investigate the effects of formoterol and salbutamol on PAF- and histamine-induced airway responses in guinea pigs.
- To compare the inhibitory potencies of these beta 2-adrenoceptor agonists against different inflammatory mediators.
Main Methods:
- Anesthetized guinea pigs were challenged with inhaled PAF or histamine.
- Lung resistance (RL) and airway microvascular leakage (Evans blue dye extravasation) were measured.
- The effects of inhaled formoterol and salbutamol were assessed.
Main Results:
- Both PAF and histamine induced significant increases in RL and microvascular leakage.
- Formoterol and salbutamol partially inhibited PAF-induced responses, with formoterol showing greater efficacy.
- These beta 2-adrenoceptor agonists inhibited histamine-induced airway effects to a greater extent.
Conclusions:
- Formoterol and salbutamol demonstrate partial inhibitory effects on airway microvascular leakage and bronchoconstriction.
- The efficacy of beta 2-adrenoceptor agonists may be influenced by the specific inflammatory mediator triggering the airway response.