Skip to main content
SpringerLink
Log in

Tissue and blood levels of zinc, copper, and magnesium in nitric oxide synthase blockade-induced hypertension

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

The aim of this study was to determine the levels of tissue and blood zinc (Zn), copper (Cu), magnesium (Mg) in nitric oxide (NO) synthase blockade-induced hypertension. A group of albino rats received a NO synthase inhibitor, N G-nitro-l-arginine-methyl ester (l-NAME, 60 mg/kg/d) in their drinking water for 21 d. l-NAME intake caused a progressive rise in this group’s resting mean arterial blood pressure compared to a control group (p<0.01). There were no differences between the groups with regard to tissue and blood levels of Zn or Cu; however, Mg concentrations were significantly lower in the hypertensive rats’ erythrocytes (20.2% reduction from control levels), cerebral cortex (17.0%), heart (9.1%), renal cortex (12%), renal medulla (16.7%), and in the tissues of the caval vein (23.7%), mesenteric artery (29.8%), renal artery (18.4%), and renal vein (22.1%). There were no significant Mg concentration changes in the hypertensive group’s plasma, cerebellum, liver, duodenum, or aortal tissue. These findings suggest that Mg depletion may play a role in the blood pressure rise that occurs in the model of chronic NO synthase inhibition-induced hypertension.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. J. Navarro, A. Sanchez, J. Saiz, L. M. Ruilope, J. Garcia-Estan, C. Romero, et al., Hormonal, renal, and metabolic alterations during hypertension induced by chronic inhibition of NO in rats, Am. J. Physiol. 267, R1516-R1521 (1994).

    PubMed  CAS  Google Scholar 

  2. M. O. Riberio, E. Antunes, G. Nucci, S. M. Lovisolo, and R. Zatz, Chronic inhibition of nitric oxide synthesis, a new model of arterial hypertension, Hypertension 20, 298–303 (1992).

    Google Scholar 

  3. Jr R. D. Manning, L. Hu, and J. F. Reckelhoff, Role of nitric oxide in arterial pressure and renal adaptations to long-term changes in sodium intake, Am. J. Physiol. 272, R1162-R1169 (1997).

    PubMed  CAS  Google Scholar 

  4. G. Frithz and G. Ronquist, Increased red cell content of Zn2+ in essential hypertension, Acta Med. Scand. 205, 647–649 (1979).

    Article  PubMed  CAS  Google Scholar 

  5. J. G. Henrotte, M. Santarromana, G. Franck, and R. Bourdon, Blood and tissue zinc levels in spontaneously hypertensive rats, J. Am. Coll. Nutr. 9, 340–343 (1990).

    PubMed  CAS  Google Scholar 

  6. G. Vivoli, P. Borella, P. Bergomi, and G. Fantuzzi, Zinc and copper levels in serum, urine, and hair of humans in relation to blood pressure, Sci. Total Environ. 66, 55–64 (1987).

    Article  PubMed  CAS  Google Scholar 

  7. A. Berthelot, C. Luthringer, and A. Exinger, Trace elements during the development of hypertension in the spontaneously hypertensive rat, Clin. Sci. 72, 515–518 (1987).

    PubMed  CAS  Google Scholar 

  8. M. S. Clegg, F. Ferrel, and C. L. Keen, Hypertension-induced alterations in copper and zinc metabolism in Dahl rats, Hypertension 9, 624–628 (1987).

    PubMed  CAS  Google Scholar 

  9. S. Wallach and R. L. Verch, Tissue magnesium in spontaneously hypertensive rats, Magnesium 5, 33–38 (1986).

    PubMed  CAS  Google Scholar 

  10. P. Laurant, J. P. Kantelip, and A. Berthelot, Dietary magnesium supplementation modifies blood pressure and cardiovascular function in mineralocorticoid-salt hypertensive rats but not in normotensive rats, J. Nutr. 125, 830–841 (1995).

    PubMed  CAS  Google Scholar 

  11. H. Karppanen, Epidemiologic evidence for considering magnesium deficiency as a risk factor for cardiovascular diseases, Magnesium Bull. 12, 80–86 (1990).

    Google Scholar 

  12. I. Kaputlu, G. Sadan, B. Karayalcin, and A. Boz, Beneficial effects of pentoxifylline on cyclosporine-induced nephrotoxicity, Clin. Exp. Pharmacol. Physiol. 24, 365–369 (1997).

    PubMed  CAS  Google Scholar 

  13. B. L. Vallee and K. H. Falchuk, The biochemical basis of zinc physiology, Physiol. Rev. 73, 79–118 (1993).

    PubMed  CAS  Google Scholar 

  14. G. Leblondel and P. Allain, Altered element concentrations in tissues of spontaneously hypertensive rats, Biomed. Pharmacother. 42, 121–129 (1988).

    PubMed  CAS  Google Scholar 

  15. N. Saito, G. C. Abbu, Y. Konishi, S. Nishiyama, and T. Okada, Magnesium, calcium and trace elements in spontaneously hypertensive rats, Clin. Exp. Pharmacol. Physiol. 22(Suppl. 1), S212-S214 (1995).

    CAS  Google Scholar 

  16. J. G. Henrotte, G. Franck, M. Santarromana, and R. Bourdon, Tissue and blood magnesium levels in spontaneously hypertensive rats, at rest and stressful conditions, Magnesium Res. 4, 91–96 (1991).

    CAS  Google Scholar 

  17. R. M. Touyz, F. J. Milne, and S. G. Reinach, Intracellular Mg2+, Ca2+, Na2+ and K+ in platelets and erythrocytes of essential hypertension patients: relation to blood pressure. Clin. Exp. Hypertens. 14, 1189–1209 (1992).

    CAS  Google Scholar 

  18. K. Kisters, M. Tepel, C. Spieker, K. H. Dietl, M. Barenbrock, K. H. Rahn, et al., Decreased cellular Mg2+ concentrations in a subgroup of hypertensives-cell models for the pathogenesis of primary hypertension. J. Hum. Hypertens. 11, 367–372 (1997).

    Article  PubMed  CAS  Google Scholar 

  19. L. M. Resnick, R. K. Gupta, and J. H. Laragh, Intracellular free magnesium in erythrocytes of essential hypertension: relation to blood pressure and serum divalent cations. Proc. Natl. Acad. Sci. USA 81, 6511–6515 (1984).

    Article  PubMed  CAS  Google Scholar 

  20. S. E. Kjeldsen, O. M. Sejersted, P. Frederichsen, P. Leren, and I. K. Eide, Increased erythrocyte magnesium content in essential hypertension, Scand. J. Clin. Lab. Invest. 50, 395–400 (1990).

    PubMed  CAS  Google Scholar 

  21. R. K. Rude, Magnesium metabolism and deficiency, Endocrinol. Metab. Clin. North Am. 22, 377–395 (1993).

    PubMed  CAS  Google Scholar 

  22. T. Nakamura, A. M. Alberola, F. J. Salazar, Y. Saito, T. Kurashina, J. P. Granger, et al., Effects of renal perfusion pressure on renal interstitial hydrostatic pressure and Na+ excretion: role of endothelium-derived nitric oxide, Nephron 78, 104–111 (1998).

    Article  PubMed  CAS  Google Scholar 

  23. C. de Rouffignac, B. Mandon, M. Wittner, and A. di Stefano, Hormonal control of renal magnesium handling, Miner. Electrolyte Metab. 19, 226–231 (1993).

    PubMed  Google Scholar 

  24. F. E. Kaiser, M. Dorighi, J. Muchnick, J. E. Morley, and P. Patrick, Regulation of gonadotropins and parathyroid hormone by nitric oxide, Life Sci. 59, 987–992 (1996).

    Article  PubMed  CAS  Google Scholar 

  25. A. Zanchi, N. C. Schaad, M. C. Osterheld, E. Grouzmann, J. Nussberger, H. R. Brunner, et al., Effect of chronic NO synthase inhibition in rats on renin-angiotensin system and sympathetic nervous system, Am. J. Physiol. 268, H2267-H2273 (1995).

    PubMed  CAS  Google Scholar 

  26. M. Giordino, M. Vermeulen, A. S. Trevani, G. Dran, G. Andonegui, and J. R. Geffner, Nitric oxide synthase inhibitors enhance plasma levels of corticosterone and ACTH, Acta Physiol. Scand. 157, 259–264 (1996).

    Article  Google Scholar 

  27. M. Haluzik, J. Nedvidkova, V. Kopsky, J. Jahodova, B. Horejsi, and V. Schreiber, The changes of the thyroid function and serum testosterone levels after long-term l-NAME treatment in male rats, J. Endocrinol. Invest. 21, 234–238 (1998).

    PubMed  CAS  Google Scholar 

  28. Y. Erlich and T. Rosenthal, Chronic hypertension leads to hyperinsulinemia in Sprague-Dawley rats treated with nitric oxide synthase inhibitor, Am. J. Hypertens. 11, 1129–1133 (1998).

    Article  PubMed  CAS  Google Scholar 

  29. R. M. Mclean, Magnesium and its therapeutic uses-a review, Am. J. Med. 96, 63–76 (1994).

    Article  PubMed  CAS  Google Scholar 

  30. B.M. Altura, B.T. Altura, A. Gebrewold, H. Ising, and T. Ghünter, Magnesium deficiency and hypertension: correlation between magnesium-deficient diets and micro-circulatory changes in situ, Science 223, 1315–1317 (1984).

    Article  PubMed  CAS  Google Scholar 

  31. A. Zhang, B. T. Altura, and B. M. Altura, Endothelial cells are required for inhibition of contractile responses induced by reduction in extracellular magnesium and sodium ions in rat aortic smooth muscle. Microcirc. Endothelium Lymphatics 6, 427–435 (1990).

    PubMed  CAS  Google Scholar 

  32. C. Szabo, V. Berczi, F. Schneider, A. G. Kovach, and E. Monos, Role of endothelium in the response of the vein wall to magnesium withdrawal, Pflugers Arch. 420, 140–145 (1992).

    Article  PubMed  CAS  Google Scholar 

  33. D. D. Ku and H. S. Ann, Differential effects of magnesium on basal and agonist-induced EDRF relaxation in canine arteries, J. Cardiovasc. Pharmacol. 17, 999–1006 (1991).

    Article  PubMed  CAS  Google Scholar 

  34. I. T. Mak, A. M. Komarov, T. L. Wagner, R. E. Stafford, B. F. Dickens, and W. B. Weglicki, Enhanced NO production during Mg deficiency and its role in mediating red blood cell glutathione loss, Am. J. Physiol. 271, C385-C390 (1996).

    PubMed  CAS  Google Scholar 

  35. P. Laurant and A. Berthelot, Influence of endothelium on Mg2+-induced relaxation in noradrenaline-contracted aorta from DOCA-salt hypertensive rat, Eur. J. Pharmacol. 258, 167–172 (1994).

    Article  PubMed  CAS  Google Scholar 

  36. P. Laurant, S. Robin, and A. Berthelot, Magnesium deficiency increases vasoconstrictor activity without affecting blood pressure of aged spontaneously hypertensive rats, Magnes. Res. 10, 107–117 (1997).

    PubMed  CAS  Google Scholar 

  37. M. Adachi, Y. Nara, M. Mano, and Y. Yamori, Effect of dietary magnesium supplementation on intralymphocytic free calcium and magnesium in stroke-prone spontaneously hypertensive rats, Clin. Exp. Hypertens. 16, 317–326 (1994).

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, Akdeniz University Faculty of Medicine, Antalya, Turkey

    Ümit Kemal Şentürk, Filiz Gündüz & Oktay Kuru

  2. Department of Pharmacology, Akdeniz University Faculty of Medicine, Antalya, Turkey

    İrfan Kaputlu & Osman Gökalp

Authors
  1. Ümit Kemal Şentürk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. İrfan Kaputlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Filiz Gündüz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Oktay Kuru
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Osman Gökalp
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kemal Şentürk, Ü., Kaputlu, İ., Gündüz, F. et al. Tissue and blood levels of zinc, copper, and magnesium in nitric oxide synthase blockade-induced hypertension. Biol Trace Elem Res 77, 97–106 (2000). https://doi.org/10.1385/BTER:77:2:97

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/BTER:77:2:97

Index Entries

Search

Navigation