THE ACTIONS OF BRADYKININ AND LYS-BRADYKININ ON TRACHEAL BLOOD-FLOW AND SMOOTH-MUSCLE IN ANESTHETIZED SHEEP

The actions of bradykinin and the related compound lys-bradykinin have been studied on the tracheal circulation and tracheal smooth muscle of the sheep. Cranial tracheal arteries of ten anaesthetised and paralysed sheep were isolated and perfused at systemic arterial pressure; arterial inflow was measured with an electromagnetic flow probe. Tracheal smooth muscle tone was assessed by measuring the external diameter of the cranial trachea. Close arterial injection of bradykinin and lys-bradykinin (0.1 to 1000 pmoles) produced potent dose-dependent falls in tracheal vascular resistance: for bradykinin a maximum fall of -56.4% (52.3-60.5%, 95% confidence interval) and for lys-bradykinin - 52.8% (46.5-59.1 %). The ED50 values were 0.69 (0.51-1.32) and 1.46 (1.19-2.28) pmoles respectively. Small and inconsistent relaxation of tracheal smooth muscle was seen with the higher doses ( > 1.9 pmoles) of both kinins. Intravenous indomethacin (5mg.kg-1 increased the vasodilation produced by bradykinin and lys-bradykinin. Oxyhaemoglobin (4-mu-m at 0.35 ml.min-1) infused into the tracheal circulation almost abolished the responses to bradykinin and methacholine. The results indicate that in the sheep trachea bradykinin has little action on airway smooth muscle but is a potent dilator of the vasculature; bradykinin and lys-bradykinin are of similar potency suggesting the action may be via B2 receptors. While the vascular responses may be modulated by vasoconstrictor cyclo-oxygenase products the vasodilation is likely to be endothelium-dependent and not prostanoid-mediated.