Vascular Responses to Adrenaline in the Rat Mesocecum After Intravenous Ferrous Sulfate, Ethylenediamine Tetra-Acetate and Beta₁-Globulin

¹ From the Department of Physiology, Stanford University, Stanford, California

Vascular responses to adrenaline were tested by topical application of dilute solutions of the drug to the exposed mesocecum of rats anesthetized with urethane or pentobarbital. Intravenous injections of iron as FeSO₄ or iron-saturated beta₁-globulin raised the adrenaline threshold. Vasodepression was produced by doses ranging from 45.5–364 µg of Fe/kg in adrenodemedullated rats and from 91–748 µg/kg in unoperated rats. Adrenodemedullated rats developed respiratory embarrassment following injection of 300–400 µg of Fe/kg. Iron-binding agents including the Na or Ca salts of ethylenediamine tetra-acetic acid (EDTA) and unsaturated beta₁-globulin given intravenously to test rats lowered the adrenaline threshold. Partial saturation of EDTA with Fe in the proportions of 4 m of EDTA to 1 of Fe produced a ‘neutral’ solution; intravenous injection of this complex produced changes in adrenaline threshold similar to those found after injection of similar volumes of water. Doses of EDTA-Ca or EDTA-Na₂, given in the same amount as those that were ‘neutral’ in the presence of Fe, lowered the adrenaline threshold, and doses of FeSO₄, containing the same amount of Fe present in the ‘neutral’ EDTA complex, raised the adrenaline threshold. Plasma iron levels were found to be elevated 1 hour after injection of Fe as the beta₁-globulin complex but not after similar doses of Fe as the sulfate in Ringer's solution. It is suggested that the changes in adrenaline threshold produced by manipulating the availability of Fe in vivo may reflect altered rates of adrenaline inactivation.