INHIBITION BY SALMETEROL OF INCREASED VASCULAR-PERMEABILITY AND GRANULOCYTE ACCUMULATION IN GUINEA-PIG LUNG AND SKIN

Citation
Cj. Whelan et M. Johnson, INHIBITION BY SALMETEROL OF INCREASED VASCULAR-PERMEABILITY AND GRANULOCYTE ACCUMULATION IN GUINEA-PIG LUNG AND SKIN, British Journal of Pharmacology, 105(4), 1992, pp. 831-838
Citations number
60
Language
INGLESE
art.tipo
Article
ISSN journal
0007-1188
Volume
105
Issue
4
Year of publication
1992
Pages
831 - 838
Database
ISI
SICI code
0007-1188(1992)105:4<831:IBSOIV>2.0.ZU;2-Q
Abstract
1. The long-acting beta(2)-adrenoceptor agonist, salmeterol has been e valuated for its anti-inflammatory effects in the guinea-pig lung and skin. 2. Salmeterol, administered in bronchodilator doses to conscious guinea-pigs by both oral (0.01-1.0 mg kg-1) and inhaled (nebulizer co ncentration, 0.001-1.0 mg ml-1) routes, inhibited histamine-induced pl asma protein extravasation (PPE) into the airway lumen. 3. Inhibition of PPE by salmeterol was long-lasting (> 6 h) and inhibited by prior a dministration of propranolol (1 mg kg-1, s.c.), indicating an effect m ediated by beta-adrenoceptors. 4. Inhaled salbutamol (nebulizer concen tration, 0.001 - 1.0 mg ml-1) also inhibited PPE in guinea-pig lung bu t, in contrast to salmeterol, this effect was short-lived with substan tial loss of activity 2 h after administration. 5. Inhaled salmeterol (0.1 mg ml-1) and salbutamol (1.0 mg ml-1) inhibited the accumulation of neutrophils in guinea-pig lung in response to lipopolysaccharide (1 00-mu-g ml-1). Salmeterol, but not salbutamol, inhibited the infiltrat ion of eosinophils into the airway lumen in response to platelet activ ating factor (100-mu-g ml-1). These effects of salmeterol were blocked by prior administration of propranolol (5 mg kg-1, s.c.), indicating that they were also beta-adrenoceptor-mediated. 6. Oral salmeterol (10 mg kg-1, p.o.), but not salbutamol (10 and 100 mg kg-1, p.o.), inhibi ted zymosan-induced granulocyte accumulation and PPE in guinea-pig ski n. Lower doses of salmeterol (0.1 and 1 mg kg-1) inhibited PPE, but no t granulocyte accumulation. The effects of salmeterol were blocked by prior administration of propranolol (1 mg kg-1, s.c.). Both salmeterol and salbutamol inhibited histamine-induced PPE in guinea-pig skin. 7. Intradermal salmeterol (10(-8) mol per site), but not salbutamol, was also effective in inhibiting zymosan-induced granulocyte accumulation and PPE in guinea-pig skin. 8. It is concluded that salmeterol, at br onchodilator doses in the guinea-pig, inhibits granulocyte accumulatio n and PPE, possibly by an action on the vasculature. As this profile o f activity is not shared by the shorter-acting compound, salbutamol, i t would seem that anti-inflammatory activity is associated with beta-a drenoceptor agonism of long duration. The implications of these findin gs for the use of salmeterol in the treatment of bronchial asthma are discussed.