Cardiovascular dysfunction and hypersensitivity to sodium pentobarbital induced by chronic barium chloride ingestion.

Barium-supplemented Long-Evans hooded rats were characterized by a persistent hypertension that was evident after 1 month of barium (100 micrograms/ml mineral fortified water) treatment. Analysis of in vivo myocardial excitability, contractility, and metabolic characteristics at 16 months revealed other significant barium-induced disturbances within the cardiovascular system. The most distinctive aspect of the barium effect was a demonstrated hypersensitivity of the cardiovascular system to sodium pentobarbital. Under barbiturate anesthesia, virtually all of the myocardial contractile indices were depressed significantly in barium-exposed rats relative to the corresponding control-fed rats. The lack of a similar response to ketamine and xylazine anesthesia revealed that the cardiovascular actions of sodium pentobarbital in barium-treated rats were linked specifically to this anesthetic, and were not representative of a generalized anesthetic response. Other myocardial pathophysiologic and metabolic changes induced by barium were manifest, irrespective of the anesthetic employed. The contractile element shortening velocity of the cardiac muscle fibers was significantly slower in both groups of barium-treated rats relative to the control groups, irrespective of the anesthetic regimen. Similarly, significant disturbances in myocardial energy metabolism were detected in the barium-exposed rats which were consistent with the reduced contractile element shortening velocity. In addition, the excitability of the cardiac conduction system was depressed preferentially in the atrioventricular nodal region of hearts from barium-exposed rats. Overall, the altered cardiac contractility and excitability characteristics, the myocardial metabolic disturbances, and the hypersensitivity of the cardiovascular system to sodium pentobarbital suggest the existence of a heretofore undescribed cardiomyopathic disorder induced by chronic barium exposure. These experimental findings represent the first indication that life-long barium ingestion may have significant adverse effects on the mammalian cardiovascular system.

Effect of a second metal on cadmium-induced hypertension.

One percent salt, 1 ppm cadmium, or 1 ppm cadmium plus 1 ppm lead in drinking water caused similar mild hypertension in rats. The hypertensive effect of salt, given for 4 months beginning at weaning, disappeared when the salt was withdrawn but subsequently returned without further exposure. Rats continuously given 1 ppm cadmium during and after salt exposure were continuously hypertensive, but salt did not increase their hypertension. Rats continuously exposed to cadmium or cadmium plus lead without extra salt remained hypertensive for 20 months. Rats exposed to cadmium or cadmium plus lead for months 4 through 8 remained hypertensive after metal exposure was discontinued; addition of 0.35 ppm selenium corrected the hypertension in cadmium-fed rats but had little effect in the cadmium plus lead exposed rats.

Inhibition of cadmium-induced hypertension in rats.

In a low cadmium environment, adding 10 parts per million (ppm) of cadmium to the drinking water of rats for 3 to 18 months induced increases in systolic pressure averaging 12 to 18 mm Hg. The pressor effect of the cadmium was inhibited by adding 3.6 ppm of selenium or 200 ppm of zinc to the drinking water or by dissolving the cadmium in hard water rather than deionized water. A second experiment with 2.5 ppm of cadmium and smaller amounts of selenium and zinc was confirmatory. Exposure to 10 ppm of cadmium increased renal, hepatic, and cardiac cadmium many fold from barely detectable control levels; however, the increases were much less when the cadmium was dissolved in hard water. Cadmium exposure also increased tissue zinc by 30 to 60%. The addition of selenium to cadmium further increased cardiac cadmium, but the addition of zinc to cadmium had no further effect on tissue cadmium. Tissue selenium concentrations were suggestively but not significantly higher following selenium exposure. Cadmium alone, or combined with selenium or zinc, increased renal copper; while the combination of cadmium and selenium increased hepatic copper.

Elevated systolic pressure following chronic low-level cadmiun feeding.

Groups of 16 female Long-Evans rats received 0, 1, 2.5, 5, 10, 25, and 50 mg cadmium/liter dringking water (parts per million (ppm)), from the time they were weaned until they were 30 mo old. Systolic pressure was measured indirectly in triplicate at 6-mo intervals. Both 2.5 and 5 ppm cadmium consistently induced significant elevations in mean systolic pressure, ranging from 13 to 33 mmHg. At 6 mo, 10 and 25 ppm cadmium also induced significant elevations, whereas at 12 mo and subsequently 1 ppm cadmium induced significant elevations. With 10 ppm cadmium or less weight gain was normal and there was no evidence of cadmium toxicity. With 25 and 50 ppm cadmium weight gain was diminished, suggesting toxicity. Five rats with each level of exposure were sacrificed every 6 mo from a second population of similarly handled rats in order to determine renal cadmium concetrations. Cadmium intakes that had induced hypertension were associated with mean renal cadmium concentrations ranging from 5 to 50 mug/g kidney.