title: Comprehensive evaluation of the effects of enalapril on matrix metalloproteinases levels in hypertension.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Fontana
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Silva
authors.forename: Tatiane C
authors.initials: TC
authors.lastname: Izidoro-Toledo
authors.forename: Celso
authors.initials: C
authors.lastname: Biagi
authors.forename: Eduardo B
authors.initials: EB
authors.lastname: Oliveira
authors.forename: Raquel F
authors.initials: RF
authors.lastname: Gerlach
authors.forename: Jose E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D004656:Enalapril / Q000494:pharmacology* / Q000627:therapeutic use; D015773:Enalaprilat / Q000494:pharmacology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D019714:Tissue Inhibitor of Metalloproteinases; D004656:Enalapril; D020782:Matrix Metalloproteinases; D015773:Enalaprilat