SUMMARY Increased dietary calcium intake in the adult spontaneously hypertensive rat (SHR) has been reported to correct low serum ionized calcium concentration ([Ca ++ ]) and to result in a significant amelioration of the prevailing hypertension. In the present study we examined several parameters of calcium metabolism in young (6-week-old) SHR and compared them with those observed in normotensive Wistar-Kyoto (WKY) rats fed equal amounts of a diet containing normal quantities of calcium (0.4%, wt/wt) for 4 weeks. A separate group of SHR was placed on an equal amount of a high calcium (2.8%, wt/wt) but otherwise identical diet. In SHR and WKY eating a normal calcium diet, serum total calcium concentration was not different, but [Ca + + ] was lower in SHR (1.58 ± 0.06 vs 1.91 ± 0.07 mmol/liter, p< 0.01). Serum immunoreactive parathyroid hormone (PTH) was increased in some, but not all, SHR. No difference was noted between the two groups in the following parameters: calcium intake, serum 1,25 dihydroxycholecalciferol (1,25(OH) 2 D 3 ), urinary calcium excretion, fractional stool calcium content ([stool calcium/calcium intake] x 100), and in vitro 4SCa uptake by everted gut sacs constructed from segments of duodenum, mid-jejunum, ileum, and proximal colon. A high calcium diet corrected the abnormal serum [Ca + + ] and PTH but did not alter the progression or severity of the hypertension in SHR. A lower net weight gain was observed in SHR on a high calcium diet when compared to SHR eating normal calcium diet (9.1 ± 1.8 vs 27.0 ± 2.0 g). This was attributed, at least in part, to a consistently higher urinary sodium loss in the former group of rats (p < 0.05-0.001 throughout the study period). The progression of hypertension, even in the face of normalized serum [Ca + + ] in young SHR, suggests that low [Ca + + ] and hypertension do not have a cause-and-effect relationship. Sustained natriuresis caused by the augmented dietary calcium intake and increased urinary calcium excretion may contribute to the blood-pressure-lowering effect reported in adult SHR. (Hypertension 6: 639-646, 1984) KEY WORDS • calcium • 1,25(OH) 2 D • sodium • spontaneously hypertensive rat A LTERATIONS in calcium homeostasis in humans with essential hypertension and in spontaneously hypertensive rats (SHR) have been described in recent years.1 " 3 Similar findings in human and rat hypertension include reduced serum ionized calcium concentration [Ca ++ ], increased immunoreactive parathyroid hormone (PTH) levels, and enhanced urinary calcium excretion. Whereas a unify-
Intestinal calcium (Ca) hyperabsorption is a well-documented feature of experimental phosphorus depletion (PD). To further evaluate the effect of PD on Ca absorption we studied metabolic balance and in vitro everted duodenal sac uptake of Ca and phosphorus (P) in weanling male rats. Animals were assigned to three dietary groups: normal, 0.3% P ad libitum (NP); low, 0.03% P ad libitum (LP); and normal, 0.3% P but pair-fed with assigned LP mates (NP-PF). Results indicate that although PD led to an early but unsustained increase in 45Ca uptake by the everted duodenal sac in vitro, net intestinal Ca retention is consistently decreased in rats on the LP diet compared with rats eating either the NP or NP-PF diet. The reduction in net intestinal Ca absorption is reflected by an increase in fecal Ca, both in absolute quantities and in proportion to dietary Ca intake. The initial negative P balance after the initiation of the LP diet was promptly, albeit precariously, corrected. This was associated with a sustained increase in duodenal 32P uptake in vitro and virtual cessation of growth. Because the biosynthesis of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its accumulation in intestinal mucosa have been reported to increase with PD, our study represents an example in which the physiological interrelationship between the activity of 1,25(OH)2D3 and intestinal Ca absorption may be dissociated.
To investigate the effect of metabolic acidosis on intestinal calcium (Ca) and phosphorus (P) absorption and vitamin D metabolism, metabolic balance studies and in vitro gut sac uptake of 45Ca and [32P]phosphate were performed in rats maintained on low-Ca and moderately low-P diet and fed NH4Cl for 3 or 9 days and pair-fed controls. Plasma 1,25(OH)2D concentration was measured in the rats fed NH4Cl for 9 days and their controls. Net Ca and P absorption was 87-92% in the acidotic rats and did not differ from control. Moreover, gut sac uptakes of 45Ca and [32P]phosphate were not different from control. Plasma 1,25(OH)2D was higher in the ammonium chloride-fed rats than in controls (213 +/- 44 vs. 110 +/- 12 pg/ml), and serum P was lower in the acidotic animals (4.6 +/- 0.7 vs. 7.6 +/- 0.3 mg/dl). These data indicate that metabolic acidosis does not depress the augmented intestinal absorption of calcium and phosphorus noted during their dietary deprivation nor reduce the plasma level of 1,25(OH)2D.
We examined the effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on intestinal 45Ca and [32P]phosphate uptake in normal and mineral- and vitamin D-replete adult rats. The results indicate that 45Ca uptake by adult rat duodenum was stimulated by "physiological" doses of 1,25(OH)2D3. With increasing dosage of 1,25(OH)2D3, 45Ca uptake also became stimulated first in the colon and then in the jejunum and ileum. The increase in duodenal and jejunal 45Ca uptake was paralleled by an increase in [32P]phosphate uptake, but this parallelism was not always seen in the ileum and was never observed in the colon. The dissociated calcium and phosphate transport response to 1,25(OH)2D3 stimulation in the colon was further confirmed by the measurement of transmural fluxes using a modified Ussing technique. These responses to 1,25(OH)2D3 are similar to those observed in younger vitamin D-deficient rats. However, supraphysiological doses of 1,25(OH)2D3 caused weight loss in normal adult rats, whereas the same metabolite, even when given in large doses, led to weight gain in vitamin D-deficient rats. We propose the normal adult rat as an additional model for evaluating the biological action of 1,25(OH)2D3.
A B S T R A C T In the small intestine, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] stimulates both calcium (Ca) and inorganic phosphate (Pi) absorption. This is mediated through an increase in mucosal-toserosal flux (Jms) whereas the serosal-to-mucosal flux (Jsm) remains unchanged. We now report that in rat proximal colon, 1,25(OH)2D3 produces active Ca absorption without affecting Pi
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