title: Antihypertensive effects exerted by enalapril in mild to moderate hypertension are not associated with changes in the circulating levels of nitric oxide-related markers.
abstract: OBJECTIVE
  The antihypertensive effects of angiotensin-converting enzyme inhibitors (ACEi) are explained, at least in part, by enhanced bradykinin-dependent nitric oxide (NO) formation and decreased angiotensin II-induced oxidative stress and vasoconstriction. We examined for the first time whether treatment with enalapril increases the plasma levels of markers of NO formation and decreases oxidative stress in mild to moderate hypertensive patients.
  
  
  METHODS
  Eighteen untreated hypertensive patients were treated with enalapril 10 mg/day (n=10) or 20 mg/day (n=8) for 60 days. Eighteen normotensive healthy controls were followed for the same period. Venous blood samples were collected at baseline and after 30/60 days of treatment with enalapril. Plasma NOx (nitrites + nitrates) concentrations were determined by using the Griess reaction. Plasma nitrite and whole blood nitrite concentrations were determined by using an ozone-based chemiluminescence assay. Plasma thiobarbituric acid-reactive species (TBARS) and 8-isoprostane concentrations were determined by a fluorimetric method and by ELISA, respectively.
  
  
  RESULTS
  Treatment with enalapril decreased blood pressure in hypertensive patients. However, we found no significant changes in plasma NOx, nitrite, whole blood nitrite, and in the levels of markers of oxidative stress in both normotensive controls and hypertensive patients treated with enalapril.
  
  
  CONCLUSIONS
  Our data show that enalapril 10-20 mg/day does not affect the concentrations of relevant markers of NO formation or markers of oxidative stress in mild to moderately hypertensive subjects, despite satisfactory blood pressure control. Our findings do not rule out the possibility that ACEi may produce such effects in more severely hypertensive patients treated with higher doses of ACEi.
authors.affiliation: Department of Pharmacology, Faculty of Medicinal Sciences, University of Campinas, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Silva
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.affiliation: Department of Pharmacology, Faculty of Medicinal Sciences, University of Campinas, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Ana C T
authors.initials: ACT
authors.lastname: Palei
authors.affiliation: Department of Pharmacology, Faculty of Medicinal Sciences, University of Campinas, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Jonas T C
authors.initials: JTC
authors.lastname: Sertório
authors.affiliation: Santa Casa of Araçatuba, Araçatuba, SP, Brazil.
authors.forename: Celso
authors.initials: C
authors.lastname: Biagi
authors.affiliation: Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil. tanus@fmrp.usp.br.
authors.forename: Jose Eduardo
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004656:Enalapril / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy*; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D054316:Biomarkers, Pharmacological; D009566:Nitrates; D009573:Nitrites; D017392:Thiobarbituric Acid Reactive Substances; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D004656:Enalapril; D015237:Dinoprost