Comparative effects of calcitriol and parathyroid hormone on serum aluminum in vitamin D-depleted rabbits fed an aluminum-supplemented diet.

Under normal circumstances, the body barriers effectively limit the entry and retention of dietary aluminum. However, both parathyroid hormone (PTH) and calcitriol (physiologically active hormonal form of vitamin D3) have been reported to produce elevation of serum aluminum in animals fed an aluminum-supplemented ration. To compare the effects of calcitriol with those of PTH with reference to their putative effect to enhance aluminum absorption, an experiment was designed wherein the serum levels of both PTH and calcitriol would be changing markedly during a short time-frame. To condition the rabbits used for this comparison, they were fed a vitamin D-free diet, which caused the level of calcitriol and its precursors to decline rapidly. The calcitriol deficit together with the ensuing lack of calcium absorption resulted in a state of secondary hyperparathyroidism. Vitamin D-depletion was shown to be complete by the high level of serum PTH and a low (unmeasurable) level of serum calcitriol. To enable comparison of PTH with calcitriol, exogenous calcitriol infusion (60 IU/day) was started by osmotic pump simultaneously with the beginning of an aluminum (aluminum lactate) supplemented diet. Aliquots were collected for both serum PTH and serum calcitriol at intervals during the 7 day study. A rising serum aluminum level was highly correlated with the rising serum calcitriol level in the rabbits (r = 0.903, p = 0.036) during the first 4 days of the infusion. The mean serum aluminum levels rose nearly 13 parts per billion (ppb) in the 7 day period. Declining serum PTH (due to feedback mechanisms of calcitriol suppressing PTH synthesis) showed a negative correlation of serum aluminum and serum PTH (r = -0.959, p = < 0.01) during the first 4 days of infusion. Control rabbits (vitamin-D depleted) fed aluminum-supplemented rations have shown only a minimal transient rise in serum aluminum level which returned to the pre-test level by the end of the week. To test for any effect of PTH on serum aluminum in the absence of calcitriol, five rabbits were implanted with osmotic pumps infusing PTH (mean 6.0 U/hr) and started on an aluminum supplemented diet. These rabbits, having previously been depleted of vitamin D were already in a state of nutritional secondary hyperparathyroidism as shown by their elevated pretest PTH levels. During the 7 day infusion, the serum aluminum rose only a mean of approximately 1 part per billion (ppb).(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of calcitriol infusions on serum aluminum in vitamin D-depleted rabbits fed an aluminum-supplemented ration.

Three dosages of calcitriol (10, 30 and 60 IU/day) were given to rabbits by subcutaneously implanted osmotic pumps. The purpose was to compare the dosages with regard to their putative effect in elevating serum aluminum levels by mechanisms such as enhancing intestinal absorption, diminishing renal excretion, or others. To establish uniform levels of endogenous calcitriol and its precursors, all rabbits had been depleted of vitamin D. The depletion was demonstrated by their serum calcidiol and calcitriol levels declining to unmeasurable levels, following the regimen of a vitamin D-free diet. The 8 rabbits were then placed on an aluminum-supplemented (aluminum lactate) ration. The amount of feed (and aluminum) consumed was determined at daily intervals. Serum aluminum levels were determined at intervals during the 7 days on this regimen. In a second test, the same 8 rabbits received the same regimen but in addition were infused with 10, 30 or 60 IU calcitriol per day. It was found that the aluminum-fed rabbits receiving 60 IU/day and 30 IU/day calcitriol infusions showed statistically significantly elevated serum aluminum levels as compared to their levels without calcitriol (p = 0.0208 and p = 0.434, respectively). Rabbits receiving pumps delivering 10 IU/day while receiving the aluminum-supplemented ration showed no rise in serum aluminum with time or treatment during the 7 day study. Likewise rabbits receiving aluminum-supplemented rations without calcitriol showed only an early minimal rise in mean serum aluminum which returned to the pre-test level by the end of a week in spite of continued consumption of aluminum-supplemented rations.

Gastric antisecretory agents. 2. Antisecretory activity of 9-[(aminoalkyl)thio]-9H-xanthenes and 5-[(aminoalkyl)thio]-5H-[1]benzopyrano[2,3-b]pyridines.

A series of 9-[(aminoalkyl)thio]-9H-xanthenes (3-6) and 5-[(aminoalkyl)thio]-5H-[1]benzopyrano[2,3-b]pyridines (7-10) possessing gastric antisecretory activity in the rat and dog is described Many of the compounds possessed good activity in the pylorus-ligated rat and several inhibited histamine-stimulated gastric acid secretion in the dog. The mechanism of acid secretion inhibition is not related to anticholinergic or histamine (H2) receptor antagonism.

Effects of prostaglandin and kinin synthesis inhibitors on renal responses to furosemide in normal and low-sodium rats.

The role of renal prostaglandin (PG) and kallikrein-kinin systems in the renal effects of furosemide was assessed indirectly by using known inhibitors of synthetic pathways in conscious rats supplemented with physiological saline (2.0% body wt.). In normal rats oral pretreatment of indomethacin or meclofenamic acid (cyclooxygenase inhibitors) each at 10 mg/kg failed to alter the diuretic and natriuretic responses to furosemide (10 and 30/kg, p.o.). In contrast, the natriuretic and diuretic actions of furosemide in sodium-deficient rats were greatly inhibited by indomethacin and by meclofenamic acid independent of changes in endogenous creatinine excretion. Aprotinin (2..0 x 10(5) KIU/kg, s. c.), an inhibitor of kallikrein formation, did not impair the natriuretic and diuretic responses to furosemide in either normal or low-sodium rats. Additionally aprotonin did not influence the antagonistic effects of indomethacin against furosemide in low-sodium rats. These results suggest that the renal PG system but not the kallikreinkinin system is necessary for furosemide to produce optimal diuretic and natriuretic effects during sodium restriction.