Hypercalcemic Rats Research Articles

An investigation of the early hypercalcaemia seen after nephrectomy in rats.

ABSTRACT The concentration of calcium, magnesium and phosphate in serum was studied for 24 hours after nephrectomy in rats. An initial rise in calcium and magnesium concentration was seen whereas the phosphate concentration continued to rise. The early rise in serum calcium concentration was independent of the adrenal glands but the values after 24 hours showed subnormal serum calcium concentration in rats with intact adrenals and hypercalcaemia in rats in which the nephrectomy was done together with adrenalectomy. Acetazolamide abolished the initial hypercalcaemia seen after nephrectomy without affecting the concentration of magnesium and phosphate. A rise in the serum calcium concentration after nephrectomy was also seen in parathyroidectomized and thyro-parathyroidectomized rats. The results suggest that the initial rise in serum calcium concentration following nephrectomy is partly due to an increased parathyroid hormone activity and partly to an increased bone resorption probably induced by intracellular acidosis.

In vivo suppression of parathyroid gland ATP content by hypercalcemia.

We have measured the ATP content of individual parathyroid glands, thyroid tissue, and skeletal muscle from normal, hypocalcemic, hypercalcemic, and hypermagnesemic rats. Hypocalcemia was induced by the iv administration of calcitonin, hypercalcemia, and hypermagnesemia by the iv administration of isotonic CaCl2 and MgCl2 respectively. To prevent ATP loss, the intact tissues were frozen in situ and fixed in methanol at –20° C for several hours prior to dissection. ATP was measured by the luciferinluciferase method. Thirty minutes after the induction of hypercalcemia, a 20–30% decrease in parathyroid gland ATP was observed. Hypermagnesemia was accompanied by a lesser but qualitatively similar effect. No change was observed with hypocalcemia. The ATP concentrations of the thyroid gland and skeletal muscle were not altered in any of the experimental conditions. These data reveal a sensitive and selective influence of hypercalcemia on the energy metabolism of the parathyroid gland. (Endocrinology 90: 291, 1972)

The mineralization of hair follicle tissue. I. An in vivo study.

Previous histological investigations have shown that the hair follicle is particularly susceptible to mineralization when the skin of hypercalcaemic rats is injured. Direct chemical and X-ray diffraction analyses of follicle tissue have now confirmed this finding. As judged by increases in both calcium and phosphorus, mineral deposits began to form in hair follicle tissue 6–12 h after a mild crush injury to the skin of rats dosed with dihydrotachysterol (DHT), and 24–48 h after a similar injury to the skin of non-dosed rats. X-ray diffraction gave a diffuse apatite pattern. Within 3 h of injury there was a rise in the calcium content of follicle tissue which was not related to DHT-dosing and which was probably a reflection of calcium binding rather than mineral deposition.

Detection of a hypocalcemic factor in the urine of hypocalcemic rats.

The presence of a hypocalcemic factor in the urine of hypercalcemic inbred albino rats was investigated. Calcium-free urine specimens obtained from normocalcemic control rats, hypercalcemic intact rats and thyroparathyroidectomized hypercalcemic rats were infused into normal inbred albino rats. It was found that hypercalcemia caused the release of a hypocalcemic factor which was excreted in the urine. Thyroparathyroidectomy performed prior to hypercalcemia, boiling or tryptic digestion of the urine obtained from hypercalcemic intact rats abolished this hypocalcemic factor. The origin and the nature of the hypocalcemic factor are discussed.(Endocrinology 87:1051,1970

The effect of abnormal maternal plasma calcium levels on the offspring of rats.

SUMMARY Study of the offspring from parathyroidectomized and hypercalcaemic rats showed that both high and low levels of maternal plasma calcium produced abnormalities in the offspring. Both groups of offspring had hypocalcaemia at birth which reverted to normal by the 7th day of life. All the offspring grew poorly compared with controls. The growth defect in the offspring of the hypocalcaemic rats was reversed if the offspring were reared by normal rats, and in the offspring of the hypercalcaemic rats was accompanied by abnormalities of the fur, including focal alopecia, which reverted to normal when the offspring were weaned on to a normal diet. The calcium concentration in the milk of the hypercalcaemic rats was higher than that in the milk of normal and parathyroidectomized rats. In the rat the plasma and milk calcium levels in the mother appeared to be important in the aetiology of neonatal hypocalcaemia and growth. It is suggested that the estimation of the plasma calcium in the mother should become a routine procedure in the investigation of cases of neonatal tetany in infants.

Effect of hypocalcemia and vitamin D-induced hypercalcemia on the incidence of metastases in rats.

To evaluate the effect of serum calcium on tumor metastases, studies were done with Walker sarcoma on hypo-, normo-, and hypercalcemic rats. Hypocalcemia was produced by thyroparathyroidectomy, and hypercalcemia was produced by vitamin D3 administration. No significant difference was found on the incidence of tumor takes in any group, or at any specific serum calcium level.

Importance of the thyroid gland in the prevention of hypercalcemia in rats.

The role of the thyroid and parathyroid glands in counteracting the hypercalcemic action of exogenous parathyroid hormone was examined. Acutely parathyroidectomized, thyroparathyroidectomized, and sham-operated rats were injected either with commercial parathyroid extract or with partially purified parathyroid hormone preparation. The rats were bled 5 or 6 hr later. The serum calcium was slightly higher in the parathyroidectomized rats injected with the parathyroid hormone preparations than in the sham-operated rats injected with control solution, but never higher than in the shamoperated rats treated with hormone. In thyroparathyroidectomized rats injected with parathyroid hormone preparations the serum calcium rose sharply (3-5 mg of calcium/100 ml of serum) and the increase was significantly higher than in the other hormone-treated groups. These results provide additional evidence that the thyroid gland is important in the prevention of experimental hypercalcemia in rats, presumably by secreting thyroc...

THE EFFECTS OF CALCIUM ON PROTEIN-BINDING AND METABOLISM OF ARGININE VASOPRESSIN IN RATS.

SUMMARY Hypercalcaemia produced in rats by the intravenous injection of calcium chloride, slowed the rate of disappearance of injected vasopressin from the blood circulation. 24% of the vasopressin injected appeared in the urine of hypercalcaemic rats compared with 7 % in control animals. Vasopressin injected intravenously into control rats was distributed in a volume equal to the blood volume but when rats had been made hypercalcaemic, the theoretical volume of distribution was three to four times greater. Antidiuresis produced by injection of large doses of vasopressin into hydrated rats was little affected by changes in the blood concentration of calcium. Calcium chloride injected intravenously into hydrated rats resulted in a temporary antidiuresis. Experiments in vitro with Sephadex G-25 showed that both ox neurophysin and rat serum protein bind vasopressin and that calcium interferes with the binding. It is suggested that calcium can compete directly with vasopressin for acidic binding sites on proteins; that this can cause the release of vasopressin and alter the transport and possibly the rate of inactivation, of vasopressin.