Autoreversal of Bradykinin Response in the Perfused Isolated Canine Hind Limb

Bradykinin lowers the systemic arterial blood pressure in all animal species tested (Haddy, Emerson and others, 1970). This hypotensive effect of bradykinin es the result of a decrease in total peripheral resistance, most probably at the arteriolar level (Baez and Orkin, 1963). However, organ responses are not uniform but display a pattern of selective vasoconstriction and vasodilation (Arcidiacono, Reininger and Sapirstein, 1966). A constriction of larger veins has been observed in rat subcutaneous tissue (Rowley, 1964) and in the rabbit ear (Guth, Bobbin and others, 1966). Also the larger veins in the visceral area appear to be constricted strongly by bradykinin (Tsuru, Ishikawa and Shigei, 1974). Several authors have reported that isolated blood vessels and some vascular beds perfused with artificial fluids respond to bradykinin with constriction (Guth, Cano and Jamarillo, 1963; Moog and Fisher, 1964; Shimamoto, Numano and others, 1966; Wiegershausen, 1966; Northover, 1967). Other have observed a hypertensive response to bradykinin in nephrectomized rats, and in rats with low blood pressure (Croxatto and Belmar, 1961; Croxato, Belmar and others, 1962). Subsequently, it was reported by us that bradykinin elicits pressure increases in the blood-perfused isolated canine hind limb when injected after a large dose of histamine (Back and Wilkens, 1965). This finding was followed by our observation that bradykinin is a potent vasoconstrictor in the isolated canine hind limb when a small amount (3 mg %) of Polyox FRA, a commercially produced high molecular weight ethylene oxide polymer, is added to the circulating blood (Wilkens and Back, 1974). Since neither the vasoconstrictor action in the presence of Polyox FRA, nor the pressar effect following histamine could be abolished by alpha adrenergic blockade, we suggested that bradykinin might act on two types of receptors.