TY - JOUR
T1 - Beneficial effects of add-on hydrochlorothiazide in rats with myocardial infarction optimally treated with quinapril
AU - Westendorp, B
AU - Schoemaker, RG
AU - Buikema, H
AU - de Zeeuw, D
AU - Boomsma, F
AU - van Gilst, WH
AU - van Veldhuisen, DJ
PY - 2005/12
Y1 - 2005/12
N2 - 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 QLII+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. (c) 2004 European Society of Cardiology. Published by Elsevier B.V All rights reserved.
AB - 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 QLII+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. (c) 2004 European Society of Cardiology. Published by Elsevier B.V All rights reserved.
KW - ACE inhibition
KW - experimental myocardial infarction
KW - rat
KW - diuretic
KW - renin angiotensin system
KW - ANGIOTENSIN-CONVERTING ENZYME
KW - LEFT-VENTRICULAR DYSFUNCTION
KW - CHRONIC HEART-FAILURE
KW - LONG-TERM SURVIVAL
KW - ACE-INHIBITION
KW - NEUROHUMORAL ACTIVATION
KW - CARDIAC-HYPERTROPHY
KW - THERAPY
KW - CAPTOPRIL
KW - RESTRICTION
U2 - 10.1016/j.ejheart.2004.12.002
DO - 10.1016/j.ejheart.2004.12.002
M3 - Article
SN - 1388-9842
VL - 7
SP - 1085
EP - 1094
JO - European Journal of Heart Failure
JF - European Journal of Heart Failure
IS - 7
ER -