Hepato-Renal Factors in Circulatory Homeostasis. II. Disappearance of Hepatic Vaso-Depressor Material Following Intravenous Administration

Abstract

Recent in vivo and in vitro studies have established the existence of a hitherto unrecognized vaso-de-pressor material (VDM) which enters the blood stream in increasing amts. during the decompensatory stage of hemorrhagic and tourniquet shock. The persistence of vaso-de-pressor activity in the blood of shocked animals is in contrast to its transient effect when injected into the blood stream of normal rats for bio-assay. Expts. were carried out to determine the rate at which the endogenous and exogenous VDM was cleared from the blood stream of rabbits with the liver and kidneys intact, and with either the liver or kidneys, or both, excluded from the circulation. The exogenous VDM was concentrated and purified from saline extracts of anaerobic beef liver. The endogenous VDM was released into the blood following liver anoxia produced by temporary occlusion of the hepatic artery in a partially eviscerated prepn. The vaso-depressor activity of the heparinized plasma samples was detd. by the rat meso-appendix technique, which uses the reactivity of the terminal arterioles and precapillaries to epine-phrine as the index of vasotropic effects. Two mechanisms for VDM removal were revealed (1) its inactivation by healthy liver; (2) its excretion into the urine by normal kidney. A preliminary period of hepatic anoxia rendered the liver incapable of inactive VDM in vivo, presumably through anoxic damage to the hepatic enzyme system for this function.