EFFECT OF T-KININ ON MICROVASCULAR PERMEABILITY AND ITS MODULATION BYPEPTIDASES IN RAT AIRWAYS

T-kinin (Ile-Ser-bradykinin), the product of T-kininogen, has been fou nd in rat plasma during systemic inflammation, but the effect of this kinin on airway inflammatory response is unknown. We examined the effe ct of T-kinin on vascular permeability in airways of anesthetized rats in vivo by using photometric measurement of the extravasated Evans bl ue. Intravenous injection of T-kinin (0.1-10 mu mol/kg) increased dye extravasation in a dose-dependent manner, with 134% for trachea and 11 7% for bronchi by 1 mu mol/g. Pretreatment with bradykinin Bz-receptor antagonist Hoe-140 (100 nmol/kg), but not the B-1-receptor antagonist des-Arg(9)-Leu(8)-bradykinin (5 mg/ kg), abolished plasma extravasati on evoked by T-kinin (1 mu mol/kg). NK1 tachykinin-receptor antagonist CP-99994 (4 mg/kg) did not affect T-kinin-induced vascular leakage. P retreatment with captopril (2.5 mg/kg), angiotensin-converting enzyme inhibitor, potentiated T-kinin (100 nmol/kg)-induced plasma extravasat ion, whereas phosphoramidon (2.5 mg/kg), a neutral endopeptidase inhib itor, had no effect. We conclude that T-kinin produces airway vascular extravasation via stimulation of B-2 receptors. The effect is modulat ed by endogenous angiotensin-converting enzyme and is not mediated via activation of sensory nerve.