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. 1986 Oct;78(4):1083–1090. doi: 10.1172/JCI112664

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

K Lau, C B Langman, U Gafter, P K Dudeja, T A Brasitus
PMCID: PMC423766  PMID: 3760184

Abstract

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 [1,25(OH)2D3] 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)2D3 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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Selected References

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  1. AMES B. N., DUBIN D. T. The role of polyamines in the neutralization of bacteriophage deoxyribonucleic acid. J Biol Chem. 1960 Mar;235:769–775. [PubMed] [Google Scholar]
  2. Adams T. H., Wong R. G., Norman A. W. Studies on the mechanism of action of calciferol. II. Effects of the polyene antibiotic, filipin, on vitamin D-mediated calcium transport. J Biol Chem. 1970 Sep 10;245(17):4432–4442. [PubMed] [Google Scholar]
  3. Andrich M. P., Vanderkooi J. M. Temperature dependence of 1,6-diphenyl-1,3,5-hexatriene fluorescence in phophoslipid artificial membranes. Biochemistry. 1976 Mar 23;15(6):1257–1261. doi: 10.1021/bi00651a013. [DOI] [PubMed] [Google Scholar]
  4. Baer P. G., Bianchi G., Liliana D. Renal micropuncture study of normotensive and Milan hypertensive rats before and after development of hypertension. Kidney Int. 1978 Jun;13(6):452–466. doi: 10.1038/ki.1978.68. [DOI] [PubMed] [Google Scholar]
  5. Bhalla R. C., Webb R. C., Singh D., Ashley T., Brock T. Calcium fluxes, calcium binding, and adenosine cyclic 3',5'-monophosphate-dependent protein kinase activity in the aorta of spontaneously hypertensive and Kyoto Wistar normotensive rats. Mol Pharmacol. 1978 May;14(3):468–477. [PubMed] [Google Scholar]
  6. Bikle D. D., Whitney J., Munson S. The relationship of membrane fluidity to calcium flux in chick intestinal brush border membranes. Endocrinology. 1984 Jan;114(1):260–267. doi: 10.1210/endo-114-1-260. [DOI] [PubMed] [Google Scholar]
  7. Brasitus T. A., Schachter D. Lipid dynamics and lipid-protein interactions in rat enterocyte basolateral and microvillus membranes. Biochemistry. 1980 Jun 10;19(12):2763–2769. doi: 10.1021/bi00553a035. [DOI] [PubMed] [Google Scholar]
  8. Brasitus T. A., Schachter D., Mamouneas T. G. Functional interactions of lipids and proteins in rat intestinal microvillus membranes. Biochemistry. 1979 Sep 18;18(19):4136–4144. doi: 10.1021/bi00586a013. [DOI] [PubMed] [Google Scholar]
  9. Cadenhead D. A., Kellner B. M., Jacobson K., Papahadjopoulos D. Fluorescent probes in model membranes I: anthroyl fatty acid derivatives in monolayers and liposomes of dipalmitoylphosphatidylcholine. Biochemistry. 1977 Nov 29;16(24):5386–5392. doi: 10.1021/bi00643a034. [DOI] [PubMed] [Google Scholar]
  10. Chapman D., Penkett S. A. Nuclear magnetic resonance spectroscopic studies of the interaction of phospholipids with cholesterol. Nature. 1966 Sep 17;211(5055):1304–1305. doi: 10.1038/2111304a0. [DOI] [PubMed] [Google Scholar]
  11. Cogan U., Schachter D. Asymmetry of lipid dynamics in human erythrocyte membranes studied with impermeant fluorophores. Biochemistry. 1981 Oct 27;20(22):6396–6403. doi: 10.1021/bi00525a018. [DOI] [PubMed] [Google Scholar]
  12. Devynck M. A., Pernollet M. G., Nunez A. M., Meyer P. Analysis of calcium handling in erythrocyte membranes of genetically hypertensive rats. Hypertension. 1981 Jul-Aug;3(4):397–403. doi: 10.1161/01.hyp.3.4.397. [DOI] [PubMed] [Google Scholar]
  13. Donaldson C. L., Hulley S. B., Vogel J. M., Hattner R. S., Bayers J. H., McMillan D. E. Effect of prolonged bed rest on bone mineral. Metabolism. 1970 Dec;19(12):1071–1084. doi: 10.1016/0026-0495(70)90032-6. [DOI] [PubMed] [Google Scholar]
  14. Elgavish A., Rifkind J., Sacktor B. In vitro effects of vitamin D3 on the phospholipids of isolated renal brush border membranes. J Membr Biol. 1983;72(1-2):85–91. doi: 10.1007/BF01870316. [DOI] [PubMed] [Google Scholar]
  15. Erne P., Bolli P., Bürgisser E., Bühler F. R. Correlation of platelet calcium with blood pressure. Effect of antihypertensive therapy. N Engl J Med. 1984 Apr 26;310(17):1084–1088. doi: 10.1056/NEJM198404263101705. [DOI] [PubMed] [Google Scholar]
  16. FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
  17. Favus M. J. Factors that influence absorption and secretion of calcium in the small intestine and colon. Am J Physiol. 1985 Feb;248(2 Pt 1):G147–G157. doi: 10.1152/ajpgi.1985.248.2.G147. [DOI] [PubMed] [Google Scholar]
  18. Favus M. J., Langman C. B. Effects of 1,25-dihydroxyvitamin D3 on colonic calcium transport in vitamin D-deficient and normal rats. Am J Physiol. 1984 Mar;246(3 Pt 1):G268–G273. doi: 10.1152/ajpgi.1984.246.3.G268. [DOI] [PubMed] [Google Scholar]
  19. Fontaine O., Matsumoto T., Goodman D. B., Rasmussen H. Liponomic control of Ca2+ transport: relationship to mechanism of action of 1,25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1751–1754. doi: 10.1073/pnas.78.3.1751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gartner S. L., Vahouny G. V. Effects of epinephrine and cyclic 3',5'-AMP on perfused rat hearts. Am J Physiol. 1972 May;222(5):1121–1124. doi: 10.1152/ajplegacy.1972.222.5.1121. [DOI] [PubMed] [Google Scholar]
  21. Holmes R. P., Yoss N. L. 25-Hydroxysterols increase the permeability of liposomes to Ca2+ and other cations. Biochim Biophys Acta. 1984 Feb 29;770(1):15–21. doi: 10.1016/0005-2736(84)90067-1. [DOI] [PubMed] [Google Scholar]
  22. Jähnig F. Structural order of lipids and proteins in membranes: evaluation of fluorescence anisotropy data. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6361–6365. doi: 10.1073/pnas.76.12.6361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Katz S. S., Shipley G. G., Small D. M. Physical chemistry of the lipids of human atherosclerotic lesions. Demonstration of a lesion intermediate between fatty streaks and advanced plaques. J Clin Invest. 1976 Jul;58(1):200–211. doi: 10.1172/JCI108450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kiselev G., Minenko A., Moritz V., Oehme P. Polyphosphoinositide metabolism in erythrocytes of spontaneously hypertensive rats. Biochem Pharmacol. 1981 Apr 15;30(8):833–837. doi: 10.1016/s0006-2952(81)80003-2. [DOI] [PubMed] [Google Scholar]
  25. Koutouzov S., Marche P., Cloix J. F., Meyer P. Phospholipid phosphorylation in erythrocyte of spontaneously hypertensive rats. Am J Physiol. 1982 Oct;243(4):H590–H597. doi: 10.1152/ajpheart.1982.243.4.H590. [DOI] [PubMed] [Google Scholar]
  26. Kreutter D., Matsumoto T., Peckham R., Zawalich K., Wen W. H., Zolock D. T., Rasmussen H. The effect of essential fatty acid deficiency on the stimulation of intestinal calcium transport by 1,25-dihydroxyvitamin D3. J Biol Chem. 1983 Apr 25;258(8):4977–4981. [PubMed] [Google Scholar]
  27. Kwan C. Y., Belbeck L., Daniel E. E. Abnormal biochemistry of vascular smooth muscle plasma membrane isolated from hypertensive rats. Mol Pharmacol. 1980 Jan;17(1):137–140. [PubMed] [Google Scholar]
  28. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  29. Lau K., Eby B. The role of calcium in genetic hypertension. Hypertension. 1985 Sep-Oct;7(5):657–667. doi: 10.1161/01.hyp.7.5.657. [DOI] [PubMed] [Google Scholar]
  30. Lau K., Gafter U., Rydell D., Eby B., Pesigan M., Tropp I., Garno J., Zikos D. Evidence against the role of calcium deficiency in genetic hypertension. Hypertension. 1986 Jan;8(1):45–49. doi: 10.1161/01.hyp.8.1.45. [DOI] [PubMed] [Google Scholar]
  31. Lau K., Zikos D., Spirnak J., Eby B. Evidence for an intestinal mechanism in hypercalciuria of spontaneously hypertensive rats. Am J Physiol. 1984 Nov;247(5 Pt 1):E625–E633. doi: 10.1152/ajpendo.1984.247.5.E625. [DOI] [PubMed] [Google Scholar]
  32. Lee D. B., Brautbar N., Walling M. W., Silis V., Coburn J. W., Kleeman C. R. Effect of phosphorus depletion on intestinal calcium and phosphorus absorption. Am J Physiol. 1979 Apr;236(4):E451–E457. doi: 10.1152/ajpendo.1979.236.4.E451. [DOI] [PubMed] [Google Scholar]
  33. Lotz M., Zisman E., Bartter F. C. Evidence for a phosphorus-depletion syndrome in man. N Engl J Med. 1968 Feb 22;278(8):409–415. doi: 10.1056/NEJM196802222780802. [DOI] [PubMed] [Google Scholar]
  34. Matsumoto T., Fontaine O., Rasmussen H. Effect of 1,25-dihydroxyvitamin D3 on phospholipid metabolism in chick duodenal mucosal cell. Relationship to its mechanism of action. J Biol Chem. 1981 Apr 10;256(7):3354–3360. [PubMed] [Google Scholar]
  35. Max E. E., Goodman D. B., Rasmussen H. Purification and characterization of chick intestine brush border membrane. Effects of 1alpha(OH) vitamin D3 treatment. Biochim Biophys Acta. 1978 Aug 4;511(2):224–239. doi: 10.1016/0005-2736(78)90316-4. [DOI] [PubMed] [Google Scholar]
  36. McCarron D. A., Lucas P. A., Shneidman R. J., LaCour B., Drüeke T. Blood pressure development of the spontaneously hypertensive rat after concurrent manipulations of dietary Ca2+ and Na+. Relation to intestinal Ca2+ fluxes. J Clin Invest. 1985 Sep;76(3):1147–1154. doi: 10.1172/JCI112070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. McCarron D. A., Yung N. N., Ugoretz B. A., Krutzik S. Disturbances of calcium metabolism in the spontaneously hypertensive rat. Hypertension. 1981 May-Jun;3(3 Pt 2):I162–I167. doi: 10.1161/01.hyp.3.3_pt_2.i162. [DOI] [PubMed] [Google Scholar]
  38. Montenay-Garestier T., Aragon I., Devynck M. A., Meyer P., Helene C. Evidence for structural changes in erythrocyte membranes of spontaneously hypertension rats. A fluorescence polarization study. Biochem Biophys Res Commun. 1981 May 29;100(2):660–665. doi: 10.1016/s0006-291x(81)80226-4. [DOI] [PubMed] [Google Scholar]
  39. O'Doherty P. J. 1,25-Dihydroxyvitamin D3 increases the activity of the intestinal phosphatidylcholine deacylation-reacylation cycle. Lipids. 1979 Jan;14(1):75–77. doi: 10.1007/BF02533571. [DOI] [PubMed] [Google Scholar]
  40. Oldfield E., Chapman D. Effects of cholesterol and cholesterol derivatives on hydrocarbon chain mobility in lipids. Biochem Biophys Res Commun. 1971 May 7;43(3):610–616. doi: 10.1016/0006-291x(71)90658-9. [DOI] [PubMed] [Google Scholar]
  41. Putkey J. A., Spielvogel A. M., Sauerheber R. D., Dunlap C. S., Norman A. W. Vitamin D-mediated intestinal calcium transport. Effects of essential fatty acid deficiency and spin label studies of enterocyte membrane lipid fluidity. Biochim Biophys Acta. 1982 May 21;688(1):177–190. doi: 10.1016/0005-2736(82)90593-4. [DOI] [PubMed] [Google Scholar]
  42. Rasmussen H., Fontaine O., Max E. E., Goodman D. B. The effect of 1alpha-hydroxyvitamin D3 administration on calcium transport in chick intestine brush border membrane vesicles. J Biol Chem. 1979 Apr 25;254(8):2993–2999. [PubMed] [Google Scholar]
  43. Rasmussen H., Matsumoto T., Fontaine O., Goodman D. B. Role of changes in membrane lipid structure in the action of 1,25-dihydroxyvitamin D3. Fed Proc. 1982 Jan;41(1):72–77. [PubMed] [Google Scholar]
  44. Schachter D., Cogan U., Abbott R. E. Asymmetry of lipid dynamics in human erythrocyte membranes studied with permanent fluorophores. Biochemistry. 1982 Apr 27;21(9):2146–2150. doi: 10.1021/bi00538a025. [DOI] [PubMed] [Google Scholar]
  45. Schachter D. Fluidity and function of hepatocyte plasma membranes. Hepatology. 1984 Jan-Feb;4(1):140–151. doi: 10.1002/hep.1840040124. [DOI] [PubMed] [Google Scholar]
  46. Schachter D., Shinitzky M. Fluorescence polarization studies of rat intestinal microvillus membranes. J Clin Invest. 1977 Mar;59(3):536–548. doi: 10.1172/JCI108669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Schedl H. P., Miller D. L., Pape J. M., Horst R. L., Wilson H. D. Calcium and sodium transport and vitamin D metabolism in the spontaneously hypertensive rat. J Clin Invest. 1984 Apr;73(4):980–986. doi: 10.1172/JCI111323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Shinitzky M., Barenholz Y. Dynamics of the hydrocarbon layer in liposomes of lecithin and sphingomyelin containing dicetylphosphate. J Biol Chem. 1974 Apr 25;249(8):2652–2657. [PubMed] [Google Scholar]
  49. Stern N., Lee D. B., Silis V., Beck F. W., Deftos L., Manolagas S. C., Sowers J. R. Effects of high calcium intake on blood pressure and calcium metabolism in young SHR. Hypertension. 1984 Sep-Oct;6(5):639–646. doi: 10.1161/01.hyp.6.5.639. [DOI] [PubMed] [Google Scholar]
  50. Stewart A. F., Adler M., Byers C. M., Segre G. V., Broadus A. E. Calcium homeostasis in immobilization: an example of resorptive hypercalciuria. N Engl J Med. 1982 May 13;306(19):1136–1140. doi: 10.1056/NEJM198205133061903. [DOI] [PubMed] [Google Scholar]
  51. Storch J., Schachter D. Dietary induction of acyl chain desaturases alters the lipid composition and fluidity of rat hepatocyte plasma membranes. Biochemistry. 1984 Mar 13;23(6):1165–1170. doi: 10.1021/bi00301a021. [DOI] [PubMed] [Google Scholar]
  52. Strazzullo P., Nunziata V., Cirillo M., Giannattasio R., Ferrara L. A., Mattioli P. L., Mancini M. Abnormalities of calcium metabolism in essential hypertension. Clin Sci (Lond) 1983 Aug;65(2):137–141. doi: 10.1042/cs0650137. [DOI] [PubMed] [Google Scholar]
  53. Thulborn K. R., Tilley L. M., Sawyer W. H., Treloar F. E. The use of n-(9-anthroyloxy) fatty acids to determine fluidity and polarity gradients in phospholipid bilayers. Biochim Biophys Acta. 1979 Dec 4;558(2):166–178. doi: 10.1016/0005-2736(79)90057-9. [DOI] [PubMed] [Google Scholar]
  54. Toraason M. A., Wright G. L. Transport of calcium by duodenum of spontaneously hypertensive rat. Am J Physiol. 1981 Oct;241(4):G344–G347. doi: 10.1152/ajpgi.1981.241.4.G344. [DOI] [PubMed] [Google Scholar]
  55. Tsutsumi M., Alvarez U., Avioli L. V., Hruska K. A. Effect of 1,25-dihydroxyvitamin D3 on phospholipid composition of rat renal brush border membrane. Am J Physiol. 1985 Jul;249(1 Pt 2):F117–F123. doi: 10.1152/ajprenal.1985.249.1.F117. [DOI] [PubMed] [Google Scholar]
  56. Van Blitterswijk W. J., Van Hoeven R. P., Van der Meer B. W. Lipid structural order parameters (reciprocal of fluidity) in biomembranes derived from steady-state fluorescence polarization measurements. Biochim Biophys Acta. 1981 Jun 22;644(2):323–332. doi: 10.1016/0005-2736(81)90390-4. [DOI] [PubMed] [Google Scholar]
  57. Vanderkooi J. M., Martonosi A. Sarcoplasmic reticulum. XVI. The permeability of phosphatidyl choline vesicles for calcium. Arch Biochem Biophys. 1971 Dec;147(2):632–646. doi: 10.1016/0003-9861(71)90422-x. [DOI] [PubMed] [Google Scholar]
  58. Vincent M., de Foresta B., Gallay J., Alfsen A. Fluorescence anisotropy decays of n-(9-anthroyloxy) fatty acids in dipalmitoyl phosphatidylcholine vesicles. Localization of the effects of cholesterol addition. Biochem Biophys Res Commun. 1982 Aug;107(3):914–921. doi: 10.1016/0006-291x(82)90610-6. [DOI] [PubMed] [Google Scholar]
  59. Wei J. W., Janis R. A., Daniel E. E. Alterations in calcium transport and binding by the plasma membrane of mesenteric arteries from spontaneously hypertensive rats. Blood Vessels. 1977;14(1):55–64. doi: 10.1159/000158114. [DOI] [PubMed] [Google Scholar]
  60. Wright G. L., Rankin G. O. Concentrations of ionic and total calcium in plasma of four models of hypertension. Am J Physiol. 1982 Sep;243(3):H365–H370. doi: 10.1152/ajpheart.1982.243.3.H365. [DOI] [PubMed] [Google Scholar]
  61. Wright G. L., Toraason M. A., Barbe J. S., Crouse W. The concentrations of ionic and total calcium in plasma of the spontaneously hypertensive rat. Can J Physiol Pharmacol. 1980 Dec;58(12):1494–1499. doi: 10.1139/y80-225. [DOI] [PubMed] [Google Scholar]
  62. ZLATKIS A., ZAK B., BOYLE A. J. A new method for the direct determination of serum cholesterol. J Lab Clin Med. 1953 Mar;41(3):486–492. [PubMed] [Google Scholar]

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