A low intake of dietary cadmium induces specific dose-dependent functional and biochemical changes in the cardiovascular tissues of rats. Maximum changes occur when the cadmium intake is 10 to 20 micrograms per kilogram of body weight per day. The changes reflect the accumulation of "critical" concentrations of cadmium in the cardiovascular tissues. The biologic activity of cadmium is demonstrated for intakes that approach those of the average American adult exposed to the usual environmental concentrations of the element but not to industrial concentrations. The sensitivity of the cardiovascular system to low doses of cadmium could not be anticipated by extrapolation from data on exposure to high concentrations of cadmium. The data support the hypothesis that ingested or inhaled environmental cadmium may contribute to essential hypertension in humans.

Interest in the biologic role of trace elements prompted an investigation of their renal excretion. Preliminary qualitative analysis revealed that except for cobalt the entire first transition series of metals, namely, titanium, vanadium, chromium, manganese, iron, nickel and copper, were detectable in most human urines. In addition the heavier transition metals, molybdenum and silver, as well as the related metals, zinc, cadmium, tin and lead, were ordinarily present. A method was evolved by which the urinary concentrations of such metals could be quantitatively estimated. The procedure included initial chemical concentration followed by spectrographic analysis. Contamination was minimized by careful preparation of equipment and reagents. Since extraneous iron and copper were particularly difficult to avoid and since these two metals had frequently been studied by other techniques, no attempt was made to measure them spectrographically. The exclusion of significant positive contamination, the demonstration that the low renal excretion of cobalt permitted its use as an internal standard, and the determination of standard working curves and recovery data for each metal constituted the control data for the assay procedure. Estimations were less satisfactory for chromium and titanium than for the remaining nine metals.Collection and assay of 24 hour urines were performed in a standard manner. Such urines from normal persons served to indicate both the mean level and the variability of excretion for the nine trace metals which could be satisfactorily estimated. Daily differences in the renal excretion of metal as well as the effects produced by * Supported by grants-in-aid from the National Heart Institute of the United States Public Health Service, the American Heart Association, the Life Insurance Medical Research Fund and Abbott Laboratories.t Established Investigator, American Heart Association. extremes of urinary volume and pH were determined for 24 hour urines from one normal individual. A brief preliminary study was made of the metallic spectrum in single specimens of urine from hospitalized African natives. Finally, metal concentration was measured in consecutive 24 hour urines from hypercholesterolemic patients before, during and after the parenteral administration of the chelating agent, disodium calcium ethylenediaminetetraacetate, which had been observed to lower the level of cholesterol in human plasma (1). METHODSPrelimintary qutalitative uirinalysis. In order to select the metals to be assayed, 40 single urine specimens from different subjects were analyzed qualitatively. Half of. the samples were obtained from normal individuals and half from hospitalized patients with atherosclerosis and hypertension. The urines were evaporated to approximately one-twentieth of their original volume, after which most of the organic material was oxidized with hydrogen peroxide. The residues were then dried, mixed with an approximately equal amount of graphite, and burned to completion in a direct current arc. The ph...

Because high barium concentrations (2-10 ppm) in human drinking water have been reported to be associated with elevated cardiovascular mortality, hypertension and other cardiovascular effects were sought in rats chronically exposed for 1-16 mo to drinking water containing 1, 10, or 100 ppm barium. From weaning, female Long-Evans rats were kept in a "low contamination" environment and fed a diet low in trace metals. Their drinking water was deionized, fortified with 5 essential trace metals, and either 0, 1, 10, or 100 ppm barium was added. Indirect systolic pressure of unanesthetized rats was measured in triplicate at 1, 2, 4, 8, 12, and 16 mo. Average systolic pressure increased significantly after exposure to 100 ppm barium for 1 mo or longer and after exposure to 10 ppm barium for 8 mo or longer. After 4 or 16 mo, barium exposure failed to alter organ weights or tissue concentrations of calcium, magnesium, sodium, or potassium; however, both 10 and 100 ppm barium resulted in significant increases in tissue barium. Rats exposed to 100 ppm Ba for 16 mo exhibited depressed rates of cardiac contraction and depressed electrical excitability in the heart. Hearts from these maximally exposed rats also had significantly lower ATP content and phosphorylation potential, as measured by 31P NMR spectroscopy. Although the barium-induced increase in the blood pressure of rats was modest, comparable mild hypertension in humans would have major health implications.

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