EFFECTS OF CROMAKALIM ON BRADYKININ-INDUCED, HISTAMINE-INDUCED AND SUBSTANCE-P-INDUCED AIRWAY MICROVASCULAR LEAKAGE IN THE GUINEA-PIG

The effects of cromakalim on the increase in microvascular permeabilit y induced by histamine, substance P or bradykinin in guinea-pig airway s were studied in vivo. Extravasation of i.v. injected Evans blue dye was used as an index of permeability. We also studied the effects of c romakalim on the contractile effect of substance P, histamine or brady kinin on the isolated guinea-pig main bronchus and on the contractile response of isolated guinea-pig main bronchi to electrical field stimu lation. Cromakalim (30 to 300 mug.kg-1) did not inhibit the increase i n microvascular permeability induced by histamine (30 mug.kg-1) in gui nea-pig airways and potentiated (30 and 100 mug.kg-1) the effects of s ubstance P (0.3 mug.kg-1) in trachea, main bronchi and proximal intrap ulmonary airways. In contrast, cromakalim (30 and 300 mug.kg-1) reduce d the increase in microvascular permeability induced by bradykinin (0. 3 mug.kg-1). However, a significant potentiation of the effects of bra dykinin was observed with cromakalim (100 mug.kg-1) in main bronchi an d intrapulmonary airways. In the isolated guinea-pig main bronchus, th e contractile effects of bradykinin, histamine and substance P were no t modified by cromakalim (10(-5) M). Conversely, cromakalim (10(-5) M) significantly reduced both cholinergic and noncholinergic contractile responses induced by electrical field stimulation of the isolated gui nea-pig main bronchus. In conclusion, cromakalim can partially inhibit the increase in microvascular permeability induced by i.v. bradykinin . It is suggested that this effect might occur through inhibition of t he nonadrenergic noncholinergic excitatory (NANC) nerves preventing re lease by bradykinin of inflammatory neuropeptides such as substance P.