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Interrelationships between experimental hypercholesteremia, magnesium requirement, and experimental atherosclerosis.

The addition of cholesterol and cholic acid to a diet containing 24 mg. percent of magnesium, an amount normally required for young rats, resulted in magnesium deficiency in rats. This was characterized by hyperexcitability, hyperemia of the ears, calcium deposition in the kidney tubules, low serum magnesium levels, and decreased oxidative phosphorylation of heart mitochondria. All these lesions were prevented by raising the dietary magnesium level four to eight times. Feeding the atherogenic diet produced the deposition of lipide in the aorta and in the heart valves. The extent of this intimal sudanophilia was reduced by large amounts of dietary magnesium although serum cholesterol values did not fall and usually rose. This represents perhaps the first clear cut disassociation between serum cholesterol values and the extent of intimal sudanophilia. Raising the level of dietary protein from 10 to 20 per cent decreased the serum cholesterol levels and the extent of the kidney lesions. Thyroxine administration lowered the serum cholesterol values, abolished the kidney lesions and reduced the intimal sudanophilia. These effects occurred even though the serum magnesium levels remained low.

Animals↗

Influence of dietary magnesium on cardiac and renal lesions of young rats fed an atherogenic diet.

Young male rats fed an atherogenic diet for 24 to 26 days developed magnesium deficiency. The renal lesions, calcium deposition in tubular lumens in the outer zona intermedia, are morphologically consistent with those seen in animals fed magnesium-free diets. It was necessary to feed 8 to 16 times the normal requirement of magnesium to prevent completely these lesions. The limitations in the pathogenesis of these renal lesions are discussed. The addition of 2 mg. per cent of thyroxine to the diet markedly lowered or abolished deposition of calcium in the kidney; it also lowered atherogenesis to a minimum but did not abolish it. Early lesions of atherosclerosis of the cardiac valves and of the aorta were observed. These were more prominent in animals on a 10 per cent than in those on a 20 per cent protein diet. The atherosclerosis was diminished but not abolished by exceedingly high dietary levels of magnesium in the 10 per cent protein group. Such a decrease was not noted in the 20 per cent protein group. There did not appear to be significant variation in the morphology of the fatty livers in and between the various groups and subgroups as judged by staining with Sudan IV.

Animals↗

The effect of external calcium and magnesium depletion on single nerve fibers.

The three types of motor axons found in the walking legs of the lobster were shown to respond differently upon exposure to calcium-free solutions. While all fiber types became more excitable initially in calcium-free solutions, only openers became spontaneously active. Fast closers showed the least reduction in rheobase value upon calcium depletion. After 5 minutes in calcium-free solution all fibers showed a rise in rheobase value, and more rapid accommodation. A natural period for spontaneous firing of opener fibers was disclosed. Following such a spontaneous discharge, low amplitude rhythmical potentials were recorded. These small potentials had the same period as the spontaneous spikes. The role of calcium ion in the excitable process was discussed. Magnesium ion was shown to act synergistically with calcium ion. All fiber types became spontaneously active in solutions deprived of both calcium and magnesium. Subsequent hypoexcitability was more pronounced in calcium- and magnesium-depleted solutions than it was in only calcium-depleted solutions.

Calcium↗