1. The effects of acute uraemia on arterial and visceral calcium concentrations were studied in acutely uraemic rats. The influences of thyroparathyroidectomy, phosphate depletion and diphosphonate therapy on extra-osseous calcium concentrations were assessed in this model. 2. Aortic and visceral calcium concentrations were greater in acutely uraemic rats than in non-uraemic rats. Both prior thyroparathyroidectomy and prior phosphate-depletion resulted in lower aortic and visceral calcium concentrations in non-uraemic rats and prevented the increase in aortic and visceral calcium concentrations with acute uraemia. Diphosphonate given for 5 days before and for 2 days after the induction of acute uraemia resulted in lower tissue calcium concentrations than in non-diphosphonate-treated acutely uraemic rats. In contrast, diphosphonate given only immediately before or only after induction of acute uraemia did not prevent the increase in extra-osseous calcium concentrations with acute uraemia. 3. It is concluded that acute uraemia results in an increase in arterial and visceral calcium concentrations. Both thyroparathyroidectomy and phosphate depletion are effective in preventing the increase in extra-osseous calcium concentrations in acute uraemia. Diphosphonates may have a future role in preventing such calcification.

1. Previous studies have shown that in thyroparathyroidectomized rats injection of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at doses that inhibit bone mineral retention (0.16 mmol = 10 mg of phosphorus/kg body wt. per day subcutaneously) leads to a decrease in the net tubular reabsorption of phosphate. 2. In the present work the tubular response to EHDP (0.16 mmol/kg body wt.) injected subcutaneously for 9 days has been localized by free-flow micropuncture in thyroparathyroidectomized rats. 3. The results show that the net tubular reabsorption of phosphate along the first portion of the (early) proximal tubule was markedly depressed in the EHDP-injected thyroparathyroidectomized rats compared with that in the pair-fed thyroparathyroidectomized control animals. In this latter group the delivery of phosphate to the distal tubule was larger than in the final urine, confirming previous reports. In the EHDP-injected thyroparathyroidectomized rats no difference in delivery of phosphate was found between the distal tubule and the final urine, suggesting that diphosphonate inhibited net reabsorption of phosphate in the terminal nephron. 4. The sites of the EHDP-induced changes in the tubular handling of phosphate were similar to those previously determined for the adaptive response to an increase in the supply of phosphate.

1. Chronic administration of 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] can normalize plasma calcium in human hypoparathyroidism and in thyroparathyroidectomized animals. The effect of 1,25(OH) 2 D 3 on plasma calcium is associated with an increase in urinary calcium excretion. In an attempt to prevent this increase, thyroparathyroidectomized rats receiving 1,25(OH) 2 D 3 were also treated with hydrochlorothiazide for 9–11 days. 2. Calcium clearance studies show that hydrochlorothiazide stimulated the tubular reabsorption of calcium in thyroparathyroidectomized rats treated with 1,25(OH) 2 D 3 . 3. Calcium balance and kinetic studies indicated that hydrochlorothiazide decreased 1,25(OH) 2 D 3 -induced hypercalciuria in thyroparathyroidectomized rats. Hydrochlorothiazide did not affect the 1,25(OH) 2 D 3 -induced increase in plasma calcium. The hypocalciuric effect of hydrochlorothiazide was not associated with significant changes in calcium deposition into or release from bone. 4. In thyroparathyroidectomized rats treated with 1,25(OH) 2 D 3 the hypocalciuric effect of hydrochlorothiazide was associated with a fall in intestinal calcium absorption. Overall, the calcium balance was unaffected. 5. Thus it appears that hydrochlorothiazide reduces the 1,25(OH) 2 D 3 -induced hypercalciuria in parathyroid hormone-deficient animals by decreasing intestinal calcium absorption. Despite the decreased absorption, hydrochlorothiazide does not reduce the 1,25(OH) 2 D 3 -induced increase in plasma calcium.

1. Selected organ-ablation experiments were performed in dogs in an attempt to identify the source of the natriuretic hormone postulated to participate in the natriuresis of blood volume expansion. 2. An isolated dog kidney perfused with blood from the femoral artery of deoxycorticosterone-loaded dogs subjected to acute volume expansion with equilibrated blood served as the bioassay system for the natriuretic factor. Four groups were studied after the following procedures: group I, no ablation; group II, thyroparathyroidectomy; group III, hypophysectomy; group IV, adrenalectomy. 3. In all groups, the administration of equilibrated blood promoted a significant increase in sodium chloride excretion in the isolated kidney. The natriuresis was unrelated to changes in glomerular filtration rate, renal blood flow, renal arterial pressure, plasma protein concentration or packed cell volume. In the absence of volume expansion, sodium chloride excretion in the isolated kidney did not change or decreased. 4. These results argue against the thyroid, parathyroid, adrenal and pituitary glands as the source of natriuretic hormone.