EFFECT OF URODILATIN ON PLATELET-ACTIVATING FACTOR-INDUCED BRONCHOCONSTRICTION, VASOCONSTRICTION AND EDEMA FORMATION IN ISOLATED RAT LUNG

In the isolated perfused rat lung, perfusion with platelet-activating factor causes bronchoconstriction, vasoconstriction and edema formatio n. The bronchoconstriction and vasoconstriction are largely mediated b y 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 th e PAF-induced alterations in lung function. Pretreatment with urodilat in (0.25 mu M or 0.75 mu M) 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 vascu lar filtration coefficient. Furthermore, urodilatin failed to affect t he release of thromboxane into the perfusate in PAF-exposed lungs. Thu s, urodilatin relaxes airway and vascular smooth muscle, but fails to reduce edema formation in PAF-perfused rat lungs.