Pflügers Archiv

, Volume 402, Issue 4, pp 341–344 | Cite as

Effect of chronic elevation of plasma calcium concentration by PTH or vitamin D3 on blood pressure and hypotensive activity of nifedipine in rats

  • F. A. M. Jonkman
  • M. J. M. C. Thoolen
  • B. Wilffert
  • A. de Jonge
  • P. B. M. W. M. Timmermans
  • P. A. van Zwieten
Heart, Circulation, Respiration and Blood; Environmental and Exercise Physiology

Abstract

The influence of a chronically elevated total plasma calcium concentration on blood pressure and heart rate was investigated in conscious normotensive rats. The plasma calcium concentration was elevated by continuous subcutaneous infusion with parathormone (PTH) after parathyreoidectomy, and by oral treatment with vitamin D3. In both groups an elevated blood pressure was observed at the 1st day of treatment only. Blood pressure was returned to pretreatment values from the second day of treatments onaards. No significant changes in heart rate, due to hypercalcaemia, were observed. In hypercalcaemic rats, the calcium entry inhibitor nifedipine proved more potent in reducing blood pressure than in normocalcaemic control animals. Hydralazine was equipotent in reducing blood pressure in both groups. It is suggested, that the vasoconstrictor effects of a chronically elevated total plasma calcium concentration in conscious rats does not obviously result in a chronically elevated blood pressure, but rather in an enhanced sensitivity of the blood pressure towards calcium entry blockade.

Key words

Parathormone Vitamin D3 Hypercalcaemia Blood pressure Nitedipine Hydralazine Conscious rats 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bekemeier H (1980) Die durch Vitamin D arteriosklerotisch genachte Ratte als Krankheitsmodell: Pathomorphologie, Pathobiochemie, Pathophysiologie und Pathopharmakologie. Wiss Z Univ Halle 29:5–40Google Scholar
  2. Causton A, Charlton B, Rose GA (1965) An improved assay for parathyroid hormone, observing the rise of serum calcium in thyroparathyroidectomized rats. J Endocrinol 33:1–12Google Scholar
  3. Christensson T, Hellström K, Wrengle B (1977) Blood pressure in subjects with hypercalcemia and primary hyperparathyroidism in a health screening program. Eur J Clin Invest 7:109Google Scholar
  4. Godfraind T, Miller RC, Socrates Lima J (1982) Selective α1-and α2-adrenoceptor agonist-induced contractions and45Ca fluxes in the rat isolated aorta. Br J Pharmacol 77:597–604Google Scholar
  5. Hellström J, Birke G, Edvall CA (1959) Hypertension in hyperparathyroidism. Br J Urol 30:13Google Scholar
  6. Kesteloot H, Geboers J (1982) Calcium and blood pressure. Lancet 8276:813–815Google Scholar
  7. Marone C, Berreta-Piccoli C, Weidman P (1980) Acute hypercalceamic hypertension in man: Role of haemodynamics, catecholamines and renin. Kidney Internat 20:92–96Google Scholar
  8. McCarron DA (1982) Low serum concentrations of ionized calcium in patients with hypertension. N Engl J Med 307:226–228Google Scholar
  9. Meel JCA, Van, de Jonge A, Wilffert B, Kalkman HO, Timmermans PBMWM, van Zwieten PA (1981) Vascular smooth muscle contraction initiated by postsynaptic α2-adrenoceptor activation is induced by an influx of extracellular calcium. Eur J Pharmacol 69:205–208Google Scholar
  10. Rambausek M, Rascher W, Kreusser W, Mann JFE, Ritz E (1983) Vascular action of parathyroid hormone (PTH). First European Meeting on Hypertension, Milan, Italy, 29th May–1st June, 1983, Abstract no 360Google Scholar
  11. Rosenthal FD, Roy S (1972) Hypertension and hyperparathyroidism. Br Med J 4:396–397Google Scholar
  12. Schleiffer R, Berthelot A, Gairard A (1979) Actions of parathormone extract on arterial blood pressure and on contraction and45Ca exchange in isolated aorta of the rat. Eur J Pharmacol 58:163–167Google Scholar
  13. Still JW, Whitcomb ER (1956) Technique for long term intubation of rat aorta. J Lab Clin Med 48:152–154Google Scholar
  14. Timmermanns PBMWM, Thoolen MJMC, De Jonge A, Wilffert B, Van Zwieten PA (1984) Calcium entry and α-adrenoceptor-mediated vasoconstriction in vivo and in vitro. In: Refsum O (ed) Role of α-adrenoceptors in cardiovascular disease (in press)Google Scholar
  15. Vlachakis ND, Frederics R, Velasquez M, Alexander N, Singer F, Maronde RF (1982) Sympathetic system function and vascular reactivity in hypercalcaemic patients. Hypertension 4:452–458Google Scholar
  16. Wallenstein SM, Zucker CL, Fleiss JL (1980) Some statistical methods useful in circulation research. Circ Res 47:1–9Google Scholar
  17. Weeks JR, Jones JA (1960) Routine measurement of arterial pressure in unanaesthetized rats. Proc Soc Exp Biol Med 194:646–648Google Scholar
  18. Weidmann P, Massry SG, Coburn JW, Maxwell MH, Atleson J, Kleeman CR (1972) Blood pressure effects of acute hypercalcemia. Ann Int Med 76:741–745Google Scholar
  19. Wright GL, Toraason MA, Barbe JS, Crouse W (1980) The concentrations of ionic and total calcium in plasma of the spontaneously hypertensive rat. Can J Physiol Pharmacol 58:1494–1499Google Scholar
  20. Zwieten PA, Van, van Meel JCA, Timmermans PBMWM (1982) Calcium antagonists and α2-adrenoceptors; possible role of extracellular calcium ions in 344-3 vasoconstriction. J Cardiovasc Pharmacol 4:273–279Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • F. A. M. Jonkman
    • 1
  • M. J. M. C. Thoolen
    • 1
  • B. Wilffert
    • 1
  • A. de Jonge
    • 1
  • P. B. M. W. M. Timmermans
    • 1
  • P. A. van Zwieten
    • 1
  1. 1.Department of Pharmacy, Division of PharmacotherapyUniversity of AmsterdamAmsterdamThe Netherlands

Personalised recommendations