Search

Long-term exposure to cadmium in drinking water can induce hypertension in rats. We have consistently observed that from 0.1 to 5 ppm cadmium in deionized drinking water fortified with five essential metals induces a significant pressor effect in female Long-Evans rats on a noncommerical, low cadmium, rye-based diet. To test the effect of diet, a commercial stock diet (Purina Rodent Lab Chow), with either fortified or plain deionized water, was begun at weaning in rats that were receiving water containing 0.1 or 1 ppm cadmium. The overall effect of substituting the stock diet for the rye diet was initially to lessen, and later to prevent entirely, the cadmium-induced pressor effect. Whereas control rats on the rye diet have a constant systolic pressure of about 100 mm Hg throughout the experiment; control rats on the stock diet had an increase in systolic pressure of about 1 mm Hg/month, perhaps because of cadmium from food which contained 10 times as much of the metal as the rye diet. (There was also a somewhat lower pressure among the cadmium-fed rats on stock diet than among those on the rye diet.) There were other (non-cadmium) differences between the stock and rye diets and between the remainder of our experimental conditions and those used by other investigators, presumably explaining the failure of some others to induce hypertension with cadmium.

To elucidate some features of the mechanism of distribution and localization of trace metals in soft mammalian tissues, we studied the simultaneous uptake and transport patterns of 2 essential metals, Zn and Mn, and 2 nonessential metals, Cd and Hg. The radioisotopes of the metals and loops of rat small intestine were used in a new in vitro perfusion method. The characteristic rates of metal uptake and metal transport varied markedly. During the first hour of perfusion, very small amounts of Zn, Hg or Cd were transported across the rat intestinal wall, whereas Mn was transported to an appreciable extent. Except for Mn, when the tissue uptake of a metal was high, its accumulation in the serosal solution was proportionately slow. The relative uptake-to-transport molar ratios for Zn, Hg, Cd and Mn were approximately 20:12:6:1, respectively. The uptake or transport of a metal was strikingly enhanced or depressed by the presence of a second metal particularly when the initial concentration of the second metal exceeded the concentration of the first. The effects of each of the chemical agents, L-ascorbate, dehydroascorbate, phlorhizin, iodoacetate and EDTA on the simultaneous uptake and transport of each of these 4 metals were measured. Zinc, Cd and Mn uptakes were depressed by L-ascorbate, dehydroascorbate or EDTA, whereas their transports were enhanced, except for Mn transport which was unaffected by L-ascorbate. Iodoacetate depressed Zn and Hg transports but markedly enhanced the uptakes of Zn, Hg, and Cd. Phlorhizin enhanced the uptake and depressed the transport of Cd nearly 3-fold. Both Zn uptake and transport were enhanced by phlorhizin. The transmural passages of this tetrad of metals Zn, Mn, Cd, and Hg are not dependent on the expenditure of metabolic energy, are not unidirectional, and are not carried against a concentration difference. Competition among these metals for uptake and transport appears to be primarily a competition for the common available uptake sites. Transport is controlled to a lesser degree by the diffusibility characteristics of the ions of the particular metal.