Increase in the systolic pressure of rats chronically fed cadmium

In our laboratory, chronically feeding cadmium to groups of rats has been reproducibly associated with average increases of 15 to 20 mm Hg in systolic pressure. A total of 497 female Long-Evans rats were continuously provided with drinking water fortified with five essential elements and containing from 0.01 to 50 ppm cadmium, as the acetate, from weaning for as long as 30 months. These rats, plus 311 matched control animals which received fortified water without added cadmium, were fed a special low-cadmium diet. All 808 rats were weighed at least monthly as a screen for cadmium toxicity, and their systolic pressures were measured every 3 or 6 months. The two lowest concentrations of cadmium tested (0.01 and 0.03 ppm) were not pressor; the three highest concentrations (10, 25, and 50 ppm) ultimately proved to be toxic. All indirect systolic pressures (each measured in triplicate) of all rats which received 0.1 to 5 ppm cadmium (i.e., nontoxic pressor doses) averaged 15.0 mm Hg more than simultaneously measured pressures of control rats. This average increase over the control pressure is extremely significant statistically, even though it seems relatively small in absolute terms. Occasionally, however, some rats had much larger than average increases in pressure; thus, 10 of 60 rats receiving from 0.1 to 0.5 ppm cadmium for 18 months had systolic pressures that were more than 50 mm Hg above the average pressure of the control rats. Cadmium-induced hypertension is not limited to females or to a particular strain. Although we have usually used one strain of female Long-Evans rat from a single source, males of the same strain and female Sprague-Dawley rats have also developed comparable hypertension. All subgroup II elements can apparently induce similar increases in systolic pressure averaging 15 to 20 mm Hg, but cadmium is pressor in much smaller amounts than mercury or zinc. Thus, to induce a demonstrable increase in pressure requires more than ten times as much divalent mercuric ion as cadmium and more than 1000 times as much zinc as cadmium. Exposure to another metal along with cadmium can markedly alter the ability of cadmium to induce hypertension. Selenium protects against the hypertension induced by twice as much cadmium. Large excesses of both zinc and copper have also inhibited the induction of hypertension by cadmium. In contrast, lead, which like cadmium, can also induce hypertension, augments rather than inhibits cadmium-induced hypertension; thus, lead and cadmium together can induce an average increase in systolic pressure in excess of 40 mm Hg, at least twice as large as is usually induced by either metal alone.