Evidence for an intestinal mechanism in hypercalciuria of spontaneously hypertensive rats

Lau, Kai; Zikos, D.; Spirnak, Joshua; Eby, B.

doi:10.1152/ajpendo.1984.247.5.e625

Cited by 32 publications

(61 citation statements)

References 7 publications

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“…Previous studies at 12 wk of age do not support the role of changes in vitamin D metabolism or sensitivity, since serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels were not measurably different (8), and the acute response to exogenous 1,25(OH)2D3 was blunted in the everted gut sac or perfused duodenum ofSHR (9). In the former study, serum concentrations of 1,25(OH)2D3 in prehypertensive SHR were however not evaluated (8).…”

Section: Introductionmentioning

confidence: 92%

“…Previous balance studies by our laboratory in the adult spontaneously hypertensive rat (SHR)' documented an increased net Ca absorption (1). These changes are associated with enhanced duodenal Ca uptake in situ and with absorptive hypercalciuria (1).…”

Section: Introductionmentioning

confidence: 97%

“…The relationship between these transport alterations and hypertension is unclear. Chronic treatment of the established hypertension failed to abolish these changes in Ca metabolism (1), suggesting that they are not consequences of hypertension.…”

Section: Introductionmentioning

confidence: 97%

“…These changes are associated with enhanced duodenal Ca uptake in situ and with absorptive hypercalciuria (1). The relationship between these transport alterations and hypertension is unclear.…”

Section: Introductionmentioning

confidence: 99%

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Increased calcium absorption in prehypertensive spontaneously hypertensive rat. Role of serum 1,25-dihydroxyvitamin D3 levels and intestinal brush border membrane fluidity.

Lau¹,

Langman²,

Gafter³

et al. 1986

J. Clin. Invest.

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Changes in Ca absorption have been described in the spontaneously hypertensive rat (SHR) compared with Wistar-Kyoto (WKy) rats. In 3.5-wk-old SHR and age-matched WKy controls, we measured direct arterial blood pressure, Ca absorption, and serum 1,25-dihydroxyvitamin D3 11,25(OH)2D31 levels and small intestine brush border membrane (BBM) fluidity and lipid composition. The two objectives were (a) to define the nature of the absorptive changes before detectable hypertension and (b) to evaluate the potential mechanism(s). We found that even at this normotensive stage (106±4 vs. 107±2 torr for the female and 109±3 vs. 104±3 torr for the male), the SHR (a) absorbed more Ca (1.46±0.06 vs. 1.14±0.08 mmol/d and 1.53±0.06 vs. 1.28±0.06 mmol/d, respectively) and retained more Ca, (b) had higher serum 1,25(OH)D3 levels (340±36 vs. 160±18 pg/ml and 230±25 vs. 150±16 pg/ml, respectively), and (c) possessed BBM with increased fluidity and with reduced fatty acyl saturation index owing to decreased stearic (32.2±2.6% vs. 38.2±0.9%) but increased linoleic acids (12.2±2.0% vs. 7.6±1.6%). These results demonstrate increased Ca absorption in prehypertensive SHR associated with increased serum 1,25(OH)2D3 levels, increased intestinal BBM fluidity, and reduced saturation index, which singly or in combination could produce the changes in intestinal Ca transport.

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Increased calcium absorption in prehypertensive spontaneously hypertensive rat. Role of serum 1,25-dihydroxyvitamin D3 levels and intestinal brush border membrane fluidity.

Lau¹,

Langman²,

Gafter³

et al. 1986

J. Clin. Invest.

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“…Calcium metabolism in SHR has been shown by several studies to be abnormal. These abnormalities include reduced serum ionized calcium, increased serum parathormone levels, hypercalciuria, and abnormal vitamin D metabolism (9)(10)(11)(12)(13)(14)(15)(16). Studies on calcium transport using in vivo and in vitro techniques, in general, have shown decreased calcium uptake by the small intestine of the SHR when compared with WKY (12,15,16,17,18).…”

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confidence: 99%

Ontogeny of Calcium Transport By Intestinal Golgi in Spontaneously Hypertensive Rats and Genetically Matched WKY Rats

Shibata

1990

Pediatr Res

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ABSTRACT. Our studies were designed to characterize calcium transport by intestinal Golgi vesicles in spontaneously hypertensive rats (SHR) and their genetically matched control, Wistar-Kyoto rats (WKY). The biochemical purity of the intestinal Golgi in SHR and WKY was validated by marker enzyme studies. Calcium uptake by Golgi vesicles represented transport into the intravesicular space as evidenced by temperature dependency and by calcium ionophore A23187-induced calcium efflux experiments. ATP-driven calcium uptake was stimulated severalfold compared with uptake in the absence of ATP and adenylyl-(/3-7-rnethylendiphosphate) (nonhydrolyzable ATP) in both SHR and WKY. ATP-dependent calcium uptake was significantly higher in WKY compared with SHR at early times points, 15 s-5 min ( p < 0.05-0.01). The initial rate of calcium uptake was linear up to 60 s. Epidemiologic studies suggested an inverse relationship between blood pressure and dietary calcium intake (1-5). Oral calcium supplementation in humans resulted in reduction in blood pressure (6). Furthermore, low serum level of ionized calcium has been described in humans with essential hyperten- Supported by Grant no. NIH HL3796 1. sion (7). These studies suggest an alteration of calcium homeostasis in humans with essential hypertension.The SHR is the most widely used animal model of human essential hypertension (8). Calcium metabolism in SHR has been shown by several studies to be abnormal. These abnormalities include reduced serum ionized calcium, increased serum parathormone levels, hypercalciuria, and abnormal vitamin D metabolism (9-16). Studies on calcium transport using in vivo and in vitro techniques, in general, have shown decreased calcium uptake by the small intestine of the SHR when compared with WKY (12,15,16,17,18). Calcium transport across the enterocyte, however, represents three steps that include: entry across brush border membrane, cytosolic movement, and exit of the basolateral membrane. To our knowledge, there are no studies to address the cytosolic movement of calcium within the enterocytes. Because the Golgi apparatus plays a major role in intracellular calcium handling (19,20) and abnormalities in intracellular calcium handling have been reported in tissues of SHR (2 I), we postulated that calcium uptake by Golgi apparatus might be abnormal.Therefore, our studies were designed to characterize calcium transport by intestinal Golgi of the SHR and their genetically matched control, WKY. Furthermore, calcium uptake was studied before (3-wk-old rats) and after development of hypertensive state (1 2-wk-old). MATERIALS AND METHODS Animals and materials.Both SHR and WKY were obtained from Taconic Farms (Germantown, NY). Adult rats (12-14 wk old) and weanling rats (21 + 1 d old) were used to prepare the intestinal Golgi vesicles. Adult and weanling rats were fed a regular diet that contained 1.2% calcium, 0.8 phosphate, and 1700 U/ 100 g of ergocalciferol (Teklad Diets, Madison, WI). 45Ca (0.37-1.5 GBq/mg) was obtained from New England Nuclear C...

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Increased plasma calcitonin levels in young spontaneously hypertensive rats: role in disturbed phosphate homeostasis

et al. 1987

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In young spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto controls (WKY) several parameters of phosphate and calcium homeostasis were determined. At 6 and 8 weeks, blood analysis revealed a significant hypophosphatemia (p less than 0.001) in SHR and twice as high plasma calcitonin levels in SHR than in WKY controls. At 8 weeks, 1,25-dihydroxycholecalciferol concentration was 20% higher in SHR (p less than 0.02) while 25-hydroxycholecalciferol was unaltered (p greater than 0.51). In addition total immunoreactive PTH, iPTH, was slightly increased (p less than 0.07) but intact PTH (1-84) (p greater than 0.90) was not significantly different from age matched WKY controls. Also at 8 weeks, a slightly reduced serum ionized Ca2+ concentration (p less than 0.001) with no change in total serum calcium was found in SHR (p greater than 0.39). Balance studies at 6 and 8 weeks of age revealed no significantly different balances for phosphate (F = 2.5, p greater than 0.10) and for calcium (F = 2.6, p greater than 0.09), although a tendency for slightly more positive balances existed in SHR when compared to WKY. However, SHR excreted significantly less phosphate in the urine than WKY control (F = 0.2, p less than 0.0009). Bone analysis was performed on femora of SHR and WKY of 6 weeks of age. Femora were significantly shorter in SHR (20.54 +/- 0.35 vs. 21.50 +/- 0.05 mm in WKY), whereas bone dry weight (127 +/- 6 vs. 107 +/- 2 mg).(ABSTRACT TRUNCATED AT 250 WORDS)

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Evidence for an intestinal mechanism in hypercalciuria of spontaneously hypertensive rats

Cited by 32 publications

References 7 publications

Increased calcium absorption in prehypertensive spontaneously hypertensive rat. Role of serum 1,25-dihydroxyvitamin D3 levels and intestinal brush border membrane fluidity.

Increased calcium absorption in prehypertensive spontaneously hypertensive rat. Role of serum 1,25-dihydroxyvitamin D3 levels and intestinal brush border membrane fluidity.

Ontogeny of Calcium Transport By Intestinal Golgi in Spontaneously Hypertensive Rats and Genetically Matched WKY Rats

Increased plasma calcitonin levels in young spontaneously hypertensive rats: role in disturbed phosphate homeostasis

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