THE DISAPPEARANCE OF BRADYKININ AND ELEDOISIN IN THE CIRCULATION AND VASCULAR BEDS OF THE CAT

Abstract

Bradykinin is short-lived in the circulation and has a half life of about 20 sec in man (Saameli & Eskes, 1962), and 16 sec in dog's blood (McCarthy, Potter & Nicolaides, 1965).Although little is known about its inactivation in the various vascular beds, Oates, Mel- mon, Sjoerdsma, Gillespie & Mason (1964) suggested that it was partially destroyed during passage from the venous to the arterial side of the circulation.Bumpus, Smeby, Page & Khairallah (1964) infused tritiated bradykinin into rats and found large quantities of labelled material in kidney, liver and urine.Another hypotensive peptide, eledoisin, is relatively stable in blood (Sicuteri, Fanciullaci, Franchi and Michelacci, 1963; Sturmer & Berde, 1963; Nobili, 1965), although Nobili (1965) has shown that it can be fairly rapidly inactivated by tissue homogenates, especially those from the kidney and the liver.We have measured the rate of inactivation of bradykinin and eledoisin in the circulating blood of cats, and have also studied their disappearance during passage through various vascular beds. METHODSCats of either sex weighing 1.5-4 kg were anaesthetized with ethyl chloride and ether; anaesthesia was then maintained with chloralose (80 mg/kg intravenously).The trachea was cannulated to facilitate artificial respiration.Fine polyethylene catheters (external diameter 0.96 mm) were tied into various arteries and veins, as detailed later.Heparin (1,000 i.u./kg intravenously) was injected through a venous cannula.Three blood bathed organs (Vane, 1964) were used to detect changes in concentration of circulating bradykinin and eledoisin.To superfuse the smooth muscle preparations, blood was taken from a cannulated artery, pumped by roller pump at 15 ml./min over three isolated organs, then collected in a reservoir and returned to a suitable vein either by gravity or by a second channel in the roller pump.In those experiments where the inactivation by blood was studied, enough silicone tubing of 3 mm internal diameter to contain 15 ml. of blood was included in the external circuit between the cannula supplying the blood and the assay organs.In this way infusions could be made either close to the assay organs (I.B.B.) or after incubation for known time intervals of up to 1 min with the circulating blood on its way through the extended external circuit (incubating circuit).The blood outside the animal was kept at 370 C. Mean blood pressure was measured with a mercury manometer from a side arm on the arterial cannula.