Skip to main content
SpringerLink
Log in

Effect of aluminum on the blood-brain barrier permeability during nitric oxide-blockade-induced chronic hypertension in rats

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

Abstract

We examined the effect of aluminum on the permeability of the blood-brain barrier (BBB) during nitric oxide-blockade-induced chronic hypertension in rats. Animals were given the inhibitor of nitric oxide synthase, l-NAME (N ω-nitro-l-arginine methyl ester), for 4 wk to induce chronic hypertension. Two groups of rats were given an intraperitoneal injection of aluminum chloride. The integrity of the BBB was assessed by a quantitative measurement for Evans blue (EB) dye. The arterial blood pressure in l-NAME- and l-NAME plus aluminum-treated animals was significantly elevated from 115±2.8 and 110±1.7 mm Hg to 174±5.2 and 175±4.8 mm Hg, respectively (p<0.01). The EB dye content in the brain regions of the rats in the l-NAME group was increased, but there was no statistical significance compared to the saline group. The extravasation of EB dye was significantly increased in the brain regions of the animals treated with aluminum compared to the rats treated with saline (p<0.05). A significantly higher EB dye content in the brain regions was observed in the l-NAME plus aluminium group compared to l-NAME, aluminum, and saline groups (p<0.01). These findings indicate that exposure to a high level of aluminum leads to an additional increase in BBB permeability where nitric oxide-blockade-induced chronic hypertension potentiates the effect of aluminum to enhance BBB permeability to EB dye.

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. R. Deloncle and P. Nicole, Aluminum: on both sides of the blood-brain barrier, in Mineral and Metal Neurotoxicology, M. Yasui, M. J. Strong, K. Ota, et al., eds., CRC, Boca Raton, FL, pp. 91–96 (1997).

    Google Scholar 

  2. R. A. Yokel, The toxicology of aluminum in the brain: a review, NeuroToxicology 21(5), 813–828 (2000).

    PubMed  CAS  Google Scholar 

  3. A. C. Alfrey, G. R. Le Gendre, and W. D. Kaehny, The dialysis encephalopathy syndrome: possible aluminum intoxication, N. Engl. J. Med. 294, 184–188 (1976).

    Article  PubMed  CAS  Google Scholar 

  4. R. A. Armstrong, S. J. Winsper, and J. A. Blair, Aluminum and Alzheimer’s disease, review of possible pathogenetic mechanisms, Dementia 7, 1–9 (1996).

    PubMed  CAS  Google Scholar 

  5. H. Aikoh and R. Nishio, Aluminium content of various canned and bottled beverages, Bull. Environ. Contam. Toxicol. 56, 1–7 (1996).

    Article  PubMed  CAS  Google Scholar 

  6. E. Altschuler, Aluminum-containing antacids as a cause of idiopathic Parkinson’s disease, Med. Hypothesis 53(1), 22–23 (1999).

    Article  CAS  Google Scholar 

  7. V. A. Granadillo, F. E. Tahan, O. Salgado, et al., The influence of the blood levels of lead, aluminum and vanadium upon the arterial hypertension, Clin. Chim. Acta 233, 47–59 (1995).

    Article  PubMed  CAS  Google Scholar 

  8. T. Minami, S. Tohno, M. Utsumi, et al., Selective accumulations of aluminum in five human arteries, Biol. Trace Element Res. 79, 29–37 (2001).

    Article  CAS  Google Scholar 

  9. J. A. Chazan, N. L. Lew, and E. G. Lowrie, Increased serum aluminum. An independent risk factor for mortality in patients undergoing long-term hemodialysis, Arch. Intern. Med. 1151(2), 319–322 (1991).

    Article  Google Scholar 

  10. W. A. Banks, Aluminum-induced neurotoxicity: alterations in membrane function at the blood brain barrier, Neurosci. Behav. Rev. 13, 47–53 (1989).

    CAS  Google Scholar 

  11. G. Y. Wen and H. M. Wisniewski, Histochemical localization of aluminum in the rabbit CNS, Acta Neuropathol. (Berl.) 68, 175–184 (1985).

    Article  CAS  Google Scholar 

  12. B. B. Johansson, Hypertension, in Introduction to the Blood-Brain Barrier: Methodology, Biology and Pathology, W. M. Pardridge, ed., Cambridge University Press, Cambridge, pp. 427–433 (1998).

    Google Scholar 

  13. K. L. Audus, J. A. Shinogle, F. L. Guillot, et al., Aluminum effects on brain microvessel endothelial cell monolayer permeability, Int. J. Pharmaceut. 45, 249–257 (1988).

    Article  CAS  Google Scholar 

  14. Y. S. Kim, M. H. Lee, and H. M. Wisniewski, Aluminum induced reversible change in permeability of the blood-brain barrier to [14C]-sucrose, Brain Res. 377, 286–291 (1986).

    Article  PubMed  CAS  Google Scholar 

  15. E. Duranti, P. Imperiali, and M. Sasdelli, Is hypertension a mortality risk factor in dialysis? Kidney Int. 55 (Suppl.) S173-S174 (1996).

    CAS  Google Scholar 

  16. E. Farkas, G. I. De Jong, E. Apro, et al., Similar ultrastructural breakdown of cerebrocortical capillaries in Alzheimer’s disease, Parkinson’s disease, and experimental hypertension, Ann. NY Acad. Sci. 902, 72–82 (2000).

    Article  Google Scholar 

  17. M. Kaya, M. Küçük, R. B. Kalayci, et al., Magnesium sulfate attenuates increased blood-brain barrier permeability during insulin-induced hypoglycemia in rats, Can. J. Physiol. Pharmacol. 79, 793–798 (2001).

    Article  PubMed  CAS  Google Scholar 

  18. S. Mikawa, M. D. Kinouchi, H. Kamii, et al., Attenuation of acute and chronic damage following traumatic brain injury in copper, zinc-superoxide dismutase transgenic mice, J. Neurosurg. 85, 885–891 (1996).

    Article  PubMed  CAS  Google Scholar 

  19. W. Banks and A. Kastin, Aluminum increases permeability of the blood-brain barrier to labelled DSIP and β-endorphine: possible implications for senile and dialysis dementia, Lancet 26, 1227–1229 (1983).

    Article  Google Scholar 

  20. Z. Deng, C. Coudray, L. Gouzoux, et al., Effect of oral aluminum and aluminum citrate on blood level and short-term tissue distribution of aluminum in the rat, Biol. Trace Element Res. 63, 139–147 (1998).

    CAS  Google Scholar 

  21. M. Favarato, P. Zatta, M. Perazzolo, et al., Aluminum(III) influences the permeability of the blood-brain barrier to [14C] sucrose in rats, Brain Res. 569, 330–335 (1992).

    Article  PubMed  CAS  Google Scholar 

  22. A. Iregren, B. Sjögren, K. Gustafsson, et al., Effect of the nervous system in different groups of workers exposed to aluminum, Occup. Environ. Med. 58, 453–460 (2001).

    Article  PubMed  CAS  Google Scholar 

  23. M. Küçük, R. B. Kalayci, A. Çevik, et al., Effect of aluminum on the blood-brain barrier permeability in acute and chronically hyperglycemic rats, Biol. Trace Element Res. 80, 181–189 (2001).

    Article  Google Scholar 

  24. C. Pakulski, L. Drobnik, and B. Millo, Age and sex as factors modifying the function of the blood-cerebrospinal fluid barrier, Med. Sci. Monit. 6(2), 314–318 (2000).

    PubMed  CAS  Google Scholar 

  25. A. Saija, P. Princi, N. D’Amico, et al., Aging and sex influence the permeability of the blood-brain barrier in the rat, Life Sci. 47(24), 2261–2267 (1990).

    Article  PubMed  CAS  Google Scholar 

  26. V. Stefanovich and F. Joo, Effect of propentofylline on the biochemical lesion of the rat brain in aluminum-induced neurotoxicity, Metab. Brain. Dis. 5(1), 7–17 (1990).

    Article  PubMed  CAS  Google Scholar 

  27. B. B. Johansson, Hypertension mechanisms causing stroke, Clin. Exp. Pharmacol. Physiol. 26, 563–565 (1999).

    Article  PubMed  CAS  Google Scholar 

  28. C. Berry, C. A. Hamilton, M. J. Brosnan, et al., Investigation into the sources of superoxide in human blood vessels, Circulation 101(18), 2206–2212 (2000).

    PubMed  CAS  Google Scholar 

  29. W. Gonzales, V. Fontaine, M. E. Pueyo, et al., Molecular plasticity of vascular wall during N-nitro-l-arginine methyl ester-induced hypertension, Hypertension 36, 103–109 (2000).

    Google Scholar 

  30. X. Zhang and E. F. Ellis, Superoxide dismutase reduces permeability and edema induced by hypertension in rats, Am. J. Physiol. 259(28), H497-H502 (1990).

    PubMed  CAS  Google Scholar 

  31. J. M. C. Gutteridge, G. J. Quinlan, I. Clark, et al., Aluminum salts accelerate peroxidation of membrane lipids stimulated by iron salts, Biochim. Biophysic. Acta 835, 441–447 (1985).

    CAS  Google Scholar 

  32. S. C. Bondy, S. F. Ali, and S. Guo-Ross, Aluminum but not iron treatment induces pro-oxidant events in the rat brain, Mol. Chem. Neuropathol. 34, 219–231 (1998).

    PubMed  CAS  Google Scholar 

  33. M. Yasui, T. Kihira, and K. Ota, Calcium, magnesium and aluminum concentrations in Parkinson’s disease, Neurotoxicology 13(3), 593–600 (1992).

    PubMed  CAS  Google Scholar 

  34. E. M. Burns, H. A. Nasrallah, M. H. Kathol, et al., Righ vs. left hemispheric blood-brain barrier permeability in schizophrenia: a dynamic computed tomographic study, Psychiatry Res. 22(3), 229–241 (1987).

    Article  PubMed  CAS  Google Scholar 

  35. R. L. Margolis and R. G. Robinson, Right and left cortical lesions asymmetrically alter cerebrovascular permeability in the rat, Brain Res. 359(1–2), 81–87 (1985).

    Article  PubMed  CAS  Google Scholar 

  36. W. G. Mayhan, Inhibition of nitric oxide synthase does not alter basal permeability of the blood-brain barrier, Brain Res. 855, 143–149 (2000).

    Article  PubMed  CAS  Google Scholar 

  37. R. Prado, B. D. Watson, J. Kuluz, et al., Endothelium-derived nitric oxide synthase inhibition—Effects on cerebral blood flow, pial artery diameter, and vascular morphology in rats, Stroke 23, 1118–1124 (1992).

    PubMed  CAS  Google Scholar 

  38. S. Nag, Cerebral endothelial mechanisms in increased permeability in chronic hypertension, Transport and Its Regulation, L. R. Drewes and A. L. Betz, eds., Frontiers in Cerebral Vascular Biology, Plenum, New York, pp. 263–266 (1993).

    Google Scholar 

  39. M. Küçük, M. Kaya, R. Kalayci, et al., Effects of losartan on the blood-brain barrier permeability in long-term nitric oxide blockade-induced hypertensive rats, Life Sci. 71(8), 937–946 (2002).

    Article  PubMed  Google Scholar 

  40. A. W. Vorbrodt, D. H. Dobrogowska, and A. S. Lossinsky, Ultracytochemical studies of the effects of aluminum on the blood-brain barrier, J. Histochem. Cytochem. 42(2), 203–212 (1994).

    PubMed  CAS  Google Scholar 

  41. M. L. Caspers, T. M. Kwaiser, M. J. Dow, et al., Control of the Na+,K+-ATPase under normal and pathological conditions, Mol. Chem. Neuropathol. 19, 65–81 (1993).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, Istabul University, Capa 34 390, Istanbul, Turkey

    M. Kaya

  2. Department of Forensic Medicine, Istanbul Medical Faculty, Istanbul University, Capa 34 390, Istanbul, Turkey

    N. Arican & I. Elmas

  3. Department of Institute for Experimental Medicine and Research, Istanbul University, Capa 34 390, Istanbul, Turkey

    R. Kalayci & M. Küçük

Authors
  1. M. Kaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Kalayci
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. Arican
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Küçük
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I. Elmas
    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

Kaya, M., Kalayci, R., Arican, N. et al. Effect of aluminum on the blood-brain barrier permeability during nitric oxide-blockade-induced chronic hypertension in rats. Biol Trace Elem Res 92, 221–230 (2003). https://doi.org/10.1385/BTER:92:3:221

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/BTER:92:3:221

Index Entries

Search

Navigation