SALMETEROL REDUCES EARLY-PHASE AND LATE-PHASE PLASMA LEAKAGE AND LEUKOCYTE ADHESION IN RAT AIRWAYS

We examined the effect of salmeterol, a long-acting beta(2)-adrenergic receptor agonist, on ovalbumin-induced plasma leakage and leukocyte a dhesion in tracheal blood vessels of unanesthetized brown Norway rats. Ovalbumin challenge of sensitized rats resulted in both early and lat e phases of plasma leakage as measured with Evans blue. The early phas e occurred during the challenge, The late phase began 2 h after the ch allenge, peaked at 4 h, and ended by 24 h. Ovalbumin challenge also in creased the number of adherent leukocytes in mucosal blood vessels at 4 h. Nebulized salmeterol (5 mg/ml for 10 min) administered before the challenge inhibited the early-phase leak by 26%, 58%, or 85%, dependi ng upon whether the interval between pretreatment and challenge was 0. 5, 1, or 4.5 h, respectively. Similarly, salmeterol pretreatment (0.05 to 5 mg/ml for 10 min) reduced the late-phase leak at 4 h. Late-phase leakage was completely blocked at concentrations of 0.5 mg/ml or grea ter. This inhibitory effect was prevented by prior injection of the be ta(2)-adrenergic receptor antagonist ICI-118,551. Salmeterol pretreatm ent also reduced the adherence of neutrophils, eosinophils, monocytes, and lymphocytes in mucosal blood vessels at 4 h. We conclude that sal meterol pretreatment can reduce the plasma leakage and leukocyte adhes ion in early- and rate-phase responses after antigen challenge through its action on beta(2) receptors.