In the isolated perfused rat lung, perfusion with platelet-activating factor causes bronchoconstriction, vasoconstriction and edema formation. The bronchoconstriction and vasoconstriction are largely mediated by thromboxane, whereas the edema formation is due to enhanced vascular permeability unrelated to eicosanoids. Since natriuretic peptides are known to relax smooth muscle and were suggested to attenuate enhanced vascular permeability, we investigated the effect of urodilatin on the PAF-induced alterations in lung function. Pretreatment with urodilatin (0.25 microM or 0.75 microM) reduced the PAF-induced increase in airway and vascular resistance by approximately 50%. Urodilatin pretreatment, however, was completely ineffective against the PAF-induced increase in weight gain and in vascular permeability, as assessed by the vascular filtration coefficient. Furthermore, urodilatin failed to affect the release of thromboxane into the perfusate in PAF-exposed lungs. Thus, urodilatin relaxes airway and vascular smooth muscle, but fails to reduce edema formation in PAF-perfused rat lungs.
A plethysmographic method was employed to assess the airway resistance of conscious, free-breathing guinea-pigs. Using this method animals sensitized by inhalation of ovalbumin and appropriate controls were assessed for their responsiveness to histamine and methacholine in vivo. The cough frequency on exposure to citric acid mist in the two groups was also assessed. Tracheal spirals from these animals were subsequently tested for their responsiveness to histamine, methacholine and prostaglandin D2 in vitro. Sensitization increased responsiveness to histamine, methacholine and citric acid in vivo but only histamine responses were affected in vitro. These changes were accompanied by a significant eosinophilia in the airways as assessed by bronchoalveolar lavage. We conclude that sensitization of the airways to ovalbumin results in responsiveness changes in bronchial smooth muscle accompanied by signs of airway inflammation.
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