title: Beneficial effects of add-on hydrochlorothiazide in rats with myocardial infarction optimally treated with quinapril.
abstract: BACKGROUND
  The antihypertensive and renoprotective effects of ACE inhibitor (ACEi) therapy are enhanced by inducing a negative sodium balance. Whether this strategy also improves outcome of chronic ACEi treatment after myocardial infarction (MI) is unknown. Therefore, we investigated whether hydrochlorothiazide (HCTZ) or dietary sodium restriction further improves survival in ACEi-treated rats with MI.
  
  
  METHODS
  MI was induced by coronary ligation. After 2 weeks rats were randomised to quinapril (QUI), HCTZ added to quinapril (QUI+HCTZ), or low sodium diet added to quinapril (QUI+LS). Survival was monitored for 62 weeks, after which left ventricular (LV) pressures were measured and blood for neurohumoral characterisation was collected. A separate group of rats, subjected to the same procedure, was evaluated after 35 weeks.
  
  
  RESULTS
  After 62 weeks, mortality was comparable in all groups. However, survival was improved by HCTZ until 35 weeks. This effect on survival was paralleled by decreased proteinuria and LV end-diastolic pressures in QUI+HCTZ rats at 35, but not 62 weeks. Plasma renin activity was significantly decreased in QUI+HCTZ rats at 35 weeks. Contrary to HCTZ, LS added to QUI caused no benefit.
  
  
  CONCLUSIONS
  Adding HCTZ, but not LS, to quinapril improved survival, neurohumoral status, and proteinuria during the early chronic phase of experimental post-MI LV dysfunction. Since no adverse effects were observed, HCTZ may safely be used to improve ACEi therapy.
authors.affiliation: Department of Clinical Pharmacology, University of Groningen, The Netherlands. b.westendrop@med.rug.nl
authors.forename: Bart
authors.initials: B
authors.lastname: Westendorp
authors.forename: Regien G
authors.initials: RG
authors.lastname: Schoemaker
authors.forename: Hendrik
authors.initials: H
authors.lastname: Buikema
authors.forename: Dick
authors.initials: D
authors.lastname: de Zeeuw
authors.forename: Frans
authors.initials: F
authors.lastname: Boomsma
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D000077583:Quinapril; D051381:Rats; D017207:Rats, Sprague-Dawley; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use*; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*; D016896:Treatment Outcome; D017725:Ventricular Pressure / Q000187:drug effects / Q000502:physiology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D049993:Sodium Chloride Symporter Inhibitors; D044005:Tetrahydroisoquinolines; D006852:Hydrochlorothiazide; D000077583:Quinapril