Beneficial effects of add-on hydrochlorothiazide in rats with myocardial infarction optimally treated with quinapril.
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.
Westendorp
Bart
B
Department of Clinical Pharmacology, University of Groningen, The Netherlands. b.westendrop@med.rug.nl
Schoemaker
Regien G
RG
Buikema
Hendrik
H
de Zeeuw
Dick
D
Boomsma
Frans
F
van Gilst
Wiek H
WH
van Veldhuisen
Dirk J
DJ
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
D000806:Angiotensin-Converting Enzyme Inhibitors; D049993:Sodium Chloride Symporter Inhibitors; D044005:Tetrahydroisoquinolines; D006852:Hydrochlorothiazide; D000077583:Quinapril