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Evidence of early involvement of matrix metalloproteinase-2 in lead-induced hypertension

  • Inorganic Compounds
  • Published:
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Abstract

Lead exposure increases blood pressure (BP) by unknown mechanisms. Many recent studies have shown the involvement of matrix metalloproteinases (MMPs) in hypertension, particularly MMP-2. In this work, we have examined whether MMP-2 levels increase with lead-induced increase in BP. We have also investigated whether doxycycline (an MMP inhibitor) affects these alterations. To this end, rats were exposed to lead (90 ppm) and treated with doxycycline or vehicle for 8 weeks. Similar aortic and whole blood lead levels were found in lead-exposed rats treated with either doxycycline or vehicle. Lead-induced increases in BP and aortic MMP-2 levels (activity, protein, and mRNA) were blunted by doxycycline. Doxycycline also prevented lead-induced increases in the MMP-2/TIMP-2 mRNA ratio. No significant changes in vascular reactivity or morphometric parameters were found. In conclusion, lead exposure increases BP and vascular MMP-2, which is blunted by doxycycline. This observation suggests that MMP-2 may play a role in lead-induced increases in BP.

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Acknowledgments

This study was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP-Brazil; FAPESP-Cinapce-Brazil), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-Brazil), and PROEX-CAPES (Brazil). We gratefully acknowledge the excellent technical support of Dimitrius Leonardo Pitol.

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None declared.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil

    Elen Rizzi, Michele M. Castro, Karla Fernandes & Jose E. Tanus-Santos

  2. Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil

    Fernando Barbosa Jr

  3. Department of Physiology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil

    Gabriel Maisonnave Arisi & Norberto Garcia-Cairasco

  4. Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil

    Lusiane M. Bendhack

  5. Department of Morphology, Stomatology and Physiology, Dental School of Ribeirao Preto, University of Sao Paulo, Av. Do Café S/N, Monte Alegre, Ribeirao Preto, 14040-904, Sao Paulo, Brazil

    Raquel F. Gerlach

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  1. Elen Rizzi
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  2. Michele M. Castro
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Correspondence to Raquel F. Gerlach.

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Rizzi, E., Castro, M.M., Fernandes, K. et al. Evidence of early involvement of matrix metalloproteinase-2 in lead-induced hypertension. Arch Toxicol 83, 439–449 (2009). https://doi.org/10.1007/s00204-008-0363-1

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  • DOI: https://doi.org/10.1007/s00204-008-0363-1

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