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Comprehensive Evaluation of the Effects of Enalapril on Matrix Metalloproteinases Levels in Hypertension

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Abstract

Purpose

Angiotensin-converting enzyme inhibitors (ACEi) may downregulate matrix metalloproteinases (MMPs). We examined whether enalapril affects MMP-2, MMP-8, and MMP-9 levels and activity, and their endogenous inhibitors (tissue inhibitors of MMPs, TIMP-1 and TIMP-2) levels in hypertensive patients. Moreover, we assessed the effects of enalaprilat on MMP-9 and TIMP-1 secretion by human endothelial cells (HUVECs).

Methods

Thirty-eight hypertensive patients received enalapril for 8 weeks and were compared with thirty-eight normotensive controls. Blood samples were collected at baseline and after treatment. Plasma ACE activity was determined by a fluorimetric assay. Plasma MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 were measured by ELISA and gelatin zymography. A fluorogenic peptide cleavage assay was used to measure MMP activity. HUVECs cells were stimulated by phorbol-12-myristate-13-acetate (PMA) and the effects of enalaprilat (10−10 to 10−6 M) on MMP-9 and TIMP-1 levels were determined.

Results

Enalapril decreased blood pressure and ACE activity in hypertensive patients (P < 0.05), but had no effects on plasma MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 levels, or MMP activity. Enalaprilat had no effects on PMA-induced increases in MMP-9 and TIMP-1 secretion by HUVECs or on MMP activity.

Conclusions

We show consistent evidence, both in vivo and in vitro, that enalapril does not affect MMPs and TIMPs levels in hypertensive patients.

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Acknowledgments

This work was supported by Fundação de Aparo a Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). We thank the staff from the Centro de Saúde de Araçatuba and Laboratório Exame (Araçatuba-Brazil) for technical support.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil

    Vanessa Fontana, Tatiane C. Izidoro-Toledo & Jose E. Tanus-Santos

  2. Department of Pharmacology, Faculty of Medicinal Sciences, State University of Campinas, Campinas, SP, Brazil

    Pamela S. Silva

  3. Santa Casa of Araçatuba, Araçatuba, SP, Brazil

    Celso Biagi

  4. Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil

    Eduardo B. Oliveira

  5. Department of Morphology, Estomatology and Physiology, School of Dentistry of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil

    Raquel F. Gerlach

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  1. Vanessa Fontana
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  2. Pamela S. Silva
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  7. Jose E. Tanus-Santos
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Correspondence to Jose E. Tanus-Santos.

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Fontana, V., Silva, P.S., Izidoro-Toledo, T.C. et al. Comprehensive Evaluation of the Effects of Enalapril on Matrix Metalloproteinases Levels in Hypertension. Cardiovasc Drugs Ther 26, 511–519 (2012). https://doi.org/10.1007/s10557-012-6420-2

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