Dietary sodium restriction specifically potentiates left ventricular ACE inhibition by zofenopril, and is associated with attenuated hypertrophic response in rats with myocardial infarction.
BACKGROUND
In patients with myocardial infarction (MI)-induced heart failure, angiotensin-converting enzyme (ACE) inhibitors are proven effective therapy in inhibiting the progression towards overt heart failure. However, the prognosis in these patients is still very poor, and optimisation of therapy is warranted. The antihypertensive and renoprotective effects of ACE inhibitors (ACE-Is) can be substantially enhanced by dietary sodium restriction. In line with the latter, the aim of the present study was to explore whether dietary sodium restriction enhances the efficacy of ACE-I after MI.


METHODS
Rats with MI-induced left ventricular (LV) dysfunction received ACE-I therapy with zofenopril (5.5 mg/kg/day orally), with or without dietary sodium restriction. ACE activity was measured in non-infarcted LV tissue, kidneys and plasma. Effects on cardiac hypertrophy were examined by means of organ weight/body weight ratios. After blood pressure (BP) measurements, functional consequences of therapy were evaluated as LV pressure development in isolated perfused hearts.


RESULTS
Dietary sodium restriction alone had no effect on any of the measured parameters, whereas zofenopril alone significantly reduced plasma and kidney ACE activity, but not LV ACE activity, nor LV weight/body weight ratio. However, only when ACE-I therapy was combined with dietary sodium restriction was LV ACE activity significantly reduced. This effect was paralleled by inhibition of LV hypertrophy. BP was reduced after infarction, and further reduced by zofenopril, but not affected by dietary sodium. Neither treatment was associated with effects on the MI-induced reduction of LV function in vitro.


CONCLUSIONS
Effects of ACE inhibition with zofenopril can be potentiated by additional dietary sodium restriction. However, these effects were tissue-specific, since LV, but not kidney or plasma, ACE activity was affected by the additional dietary sodium restriction. Effects on LV ACE activity were paralleled by reduced LV hypertrophy. Since the measured parameters did not indicate any adverse side-effects, dietary sodium restriction may provide a safe strategy to improve ACE-I efficacy in patients with infarction-induced LV dysfunction.
Westendorp
Bart
B
Department of Clinical Pharmacology, University of Groningen, Groningen, The Netherlands. b.westendorp@med.rug.nl
Schoemaker
Regien G
RG
Buikema
Hendrik
H
de Zeeuw
Dick
D
van Veldhuisen
Dirk J
DJ
van Gilst
Wiek H
WH
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004039:Diet, Sodium-Restricted; D006352:Heart Ventricles; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000517:prevention & control; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; C044958:zofenopril; D002216:Captopril; D007703:Peptidyl-Dipeptidase A