Long-term Calcium Research Articles

Nitrendipine, a calcium-entry blocker. Renal and humoral effects in human arterial hypertension.

Thirteen patients with hypertension and normal renal function received nitrendipine, a calcium entry blocker. Nitrendipine did not modify renal blood flow (RBF) or glomerular filtration rate (GFR), decreased mean arterial pressure (MAP) and total peripheral resistance, and did not significantly change cardiac output. Individual RBF changes did not correlate with MAP or cardiac output modifications. Mean arterial pressure changes were inversely correlated with basal renin levels and directly associated with age. Plasma catecholamines and plasma renin activity increased, but plasma aldosterone and plasma volume did not change significantly. However, the greater decrements of MAP tended to be associated with the greater increases in plasma volume. Data show that long-term calcium entry blockade by nitrendipine does not modify RBF or GFR despite the decreased renal perfusion pressure. Further, nitrendipine may be more effective in older patients and the presence of low renin.

Transient and sustained effects of hormones and calcium on membrane potential in a bone cell clone.

Measurements were made of the electrophysiological and cAMP response to changes in extracellular [Ca2+] and to hormone application in a bone cell clone. Both transient and long-term electrophysiological responses were studied. An increase in extracellular [Ca2+] usually resulted in a transient hyperpolarization of about 60-sec duration. In addition, increases in extracellular [Ca2+] from 0.9 to 1.8 mM and from 1.8 to 3.6 mM resulted in long-term hyperpolarization and increased potential fluctuations. Increasing bathing [Ca2+] until the membrane potential reached the K+ equilibrium level resulted in a significant decrease in fluctuations. Addition to the bathing medium of quinine, a putative blocker of the Ca2+-dependent K+ channel, resulted in long-term depolarization of the mean membrane potential, and a long-term decrease in potential fluctuations. Addition of Mg2+, a mild antagonist of Ca2+ entry into the cell, produced transient depolarization and reduction of potential fluctuations. These effects suggest that the potential fluctuations reflect cytoplasmic [Ca2+] fluctuations via Ca2+-dependent K+ membrane channels. Under an extracellular [Ca2+] of 1.8 mM, the application of prostaglandin E2 (PGE2), isoproterenol, and parathyroid hormone produced no significant effect on mean membrane potential or on the sustained potential fluctuations, but PGE2 did significantly raise intracellular cAMP. Under an increased bathing [Ca2+], significant changes in mean potential and fluctuations did occur in response to PGE2, but not in response to the other hormones, while the PGE2 effect on cAMP was not greatly changed. Hyperpolarizing transients of about 30-sec duration occurred in response to all of the hormones, particularly at an extracellular [Ca2+] of 3.6 mM. Thus, there are both transient and long-term electrophysiological responses to hormone application, with only the long-term response correlated with the production of cAMP. These electrophysiological responses may represent separate transient and long-term calcium transport responses to hormone application.

Hormonal alterations in experimental diabetes: role of a primary disturbance in calcium homeostasis.

Chronic diabetes mellitus in the rat is attended by a reduced bone turnover and growth arrest, decreased circulating immunoreactive parathyroid hormone (iPTH), and hypercorticosteronism. Since chronic insulin deficiency in the rat is associated with intestinal hyperabsorption of calcium and a positive calcium balance that may account for the decreased iPTH, as well as other hormonal alterations observed in these animals, we studied the effect of long-term (5 week) dietary calcium restriction (0.1% Ca, 0.8% P) in control and streptozotocin-induced diabetic rats. Chronic diabetic rats reared on a normal calcium (1.2% Ca) diet had increased serum calcium and phosphate (Pi) concentrations and were markedly hypercalciuric and phosphaturic compared with controls. Serum corticosterone was increased and iPTH markedly decreased in the diabetic animals. Dietary Ca restriction (0.1% Ca) decreased urinary calcium excretion and resulted in a comparable phosphaturic response in both control and diabetic rats. Moreover, although Ca restriction in diabetic animals had no appreciable effect on serum insulin, serum glucose, or urinary glucose excretion, it was associated with a marked increase in circulating iPTH; this resulted in serum concentrations comparable with that observed in control animals reared on the low Ca diet. These results support the hypothesis that the decreased circulating iPTH observed in chronic diabetic rats results predominantly from their intestinal hyperabsorption of Ca. In contrast to control animals, diabetic rats reared on a low Ca diet failed to maintain their serum Ca despite the marked increase in serum iPTH and striking decrease in calciuria, thus underscoring the reliance of these animals on intestinal hyperabsorption of Ca to maintain Ca balance under conditions of adequate Ca intake. Serum corticosterone was insignificantly altered by dietary Ca restriction in control rats; hypercorticosteronism, characteristically observed in diabetic rats, was normalized by Ca restriction. We conclude that a primary disturbance in Ca homeostasis may contribute, in part, to hormonal alterations observed in chronic experimental diabetes.

Spinal calcium changes with 1alpha-hydroxyvitamin D3.

During treatment of renal osteodystrophy with 1alpha-hydroxyvitamin D3 in eleven patients, regional changes in the skeleton have been compared with long-term calcium balance as assessed by whole-body calcium. Radial bone changes did not correlated well with calcium balance, but spinal calcium changes were of a similar magnitude when changes were large. Bone alkaline phosphatase changes correlated well with changes in spinal calcium, but less well with changes in radial bone density.

Total body calcium and long-term calcium balance in chronic renal disease.

Abstract Renal bone disease is a common cause of morbidity in patients with end-stage renal failure undergoing dialysis. The natural history of this entity and the effect of dialysate calcium concentrations have been studied in 26 chronic dialysis patients by total body calcium (TBC) measurement with neutron activation analysis (NAA), bone biopsies, calcium absorption, hand radiographs, serum chemistry, and skin calcium determinations. Calcium balance was measured by serial NAA over intervals up to 27 months. Total body calcium (TBC) ranged from 503 to 1,392 Gm. and in the 24 males averaged 1,116 Gm. or 96 ± 12 per cent of predicted normal. Bone fractures occurred in 5 of 8 patients with TBC less than 90 per cent of predicted normal and in only 2 of 16 patients with TBC greater than 90 per cent of predicted normal. The relationship of TBC and calcium balance with bone biopsy suggested that osteomalacia and fibrosis may be different disease entities. Osteomalacia was characterized by low TBC (87 per cent of predicted normal) and progressively negative calcium balance (−5.0 per cent TBC per year). Fibrosis was characterized by normal to high TBC (106 per cent of predicted normal) and stable calcium balance (−0.2 per cent TBC per year). A change in dialysate calcium from 3.0 to 4.0 mEq. per liter appeared to have a beneficial effect on calcium balance. Eleven patients observed on a dialysate bath of 3.0 mEq. per liter calcium over 12.2 patient-years experienced a cumulative TBC loss of 34.1 per cent. On the other hand, 10 patients observed on a 4.0 mEq. per liter calcium dialysate over 10.3 patient-years experienced a cumulative gain in TBC of 2.3 per cent.

Uterine calcium-binding protein in the laying fowl

1. 1. Intestinal and uterine calcium-binding protein (CaBP) in the fowl ( Gallus domesticus) were compared by the Chelex assay and gel electrophoresis; their response to physiological and nutritional stimuli was studied. 2. 2. Molecular weight of uterine CaBP was found to be slightly higher than that of intestinal CaBP. 3. 3. Uterine and intestinal CaBP increased within 24 hr of the onset of egg production; both decreased as egg production ceased. 4. 4. Uterine CaBP level was slightly higher during periods of uterine inactivity than during periods of egg shell formation. There was no difference in uterine CaBP between laying hens which secreted heavy or light shells. 5. 5. A long-term calcium restriction did not influence uterine CaBP level. 6. 6. The similarities and differences between uterine and intestinal CaBP, and the possible role of CaBP in uterine calcium transport are discussed.

Relationship of duodenal calcium-binding protein to calcium absorption in the laying fowl

1. 1. Changes in duodenal calcium-binding protein (CaBP) in the fowl ( Gallus domesticus) were followed by the Chelex assay and gel electrophoresis. 2. 2. CaBP increased at the onset of egg production; the high level was sustained as long as egg production continued. A decrease in CaBP due to arrest of egg production occurred within 3–5 days. 3. 3. A long-term (16–32 days) calcium restriction resulted in an elevation of the CaBP level. 4. 4. There was no change in CaBP during shell formation. 5. 5. It was concluded that only some of the regulatory changes in calcium absorption in the laying fowl could be explained on the basis of changes in the CaBP level.

The relationship of dietary calcium to osteoporosis

Long-term calcium deficient diets produced osteoporosis in rats characterized by chemical, roentgenographic and microradiographic studies. A normally mineralized skeleton could be restored by feeding a dietary supplement of calcium phosphate. These observations suggest that osteoporosis in human subjects may result from prolonged minimal negative calcium balance and that calcium supplements in the diet may be used to arrest and to improve the condition if the calcium-rich diet is maintained long enough.

A critical study of the failure of a long-term calcium and phosphorus balance experiment with laying hens

A long-term calcium and phosphorus balance experiment with laying hens is described.The cumulative balances of calcium and phosphorus over a whole year were seen to be physiologically impossible.Results from other workers using short term balancescouldbe equally impossible and a similar situation has recently been noted in balance experiments with ruminants.The techniques employed in the experiment were, therefore, investigated in detail.Only systematic errors could be responsible and it was found that the most likely source of such errors was (a) the spilling of food on to the floor or into the water bowl, and (b) failure to collect all the droppings.These errors only become apparent in long-term experiments and are more pronounced when diets containing high levels of calcium and/or phosphorus are fed.

EFFECTS OF CONTRACTILE STIMULI ON EXCHANGES OF ELECTROLYTES BETWEEN UTERINE TISSUES AND A SALINE–BICARBONATE MEDIUM

(1) Evidence has been presented suggesting that progesterone pretreatment in vivo increases the rate of leakage of potassium from rabbit uterine segments into a saline–bicarbonate medium.(2) Various types of evidence indicate that in uterine tissues, the loss of potassium from cells into potassium-free solutions is increased during the contractile actions of drugs. There was no clear-cut concomitant increase in tissue sodium concentrations. The results tend to confirm previous findings indicating that increases in potassium (but not in sodium) permeability are associated with contraction of smooth muscle.(3) Epinephrine effects on potassium loss occurred only in uteri which contracted in response to epinephrine. Norepinephrine, but not iproterenol, had a similar effect. Dibenamine, alone, decreased potassium loss and partly blocked the effects of epinephrine. Direct measurement of glycogen content suggested that these findings were not related to a glycogenolytic action of the epinephrine. Rather, the effect of epinephrine to increase potassium loss seemed to be closely related to its contractile action. In long-term experiments, both epinephrine and calcium slowed the rate of K loss and of water and sodium gain. This effect also was absent in uterine tissues which were not contracted by epinephrine.