Effects of amlodipine on endothelial function in rats with chronic heart failure after experimental myocardial infarction.
In chronic heart failure, the role of endothelial dysfunction is not yet well established. As calcium metabolism plays an important role in the endothelium, it might be suggested that calcium channel blockers influence endothelial function. Although calcium channel blockers are generally contraindicated in chronic heart failure, because they are believed to stimulate neurohumoral mechanisms and to exert negative inotropic effects, recently it has been suggested that amlodipine might have a favorable affect on mortality in patients with heart failure. The mechanism of amlodipine that contributes to this beneficial effect is not known. Therefore we investigated whether 10 weeks of amlodipine treatment could influence endothelial function in rats with congestive heart failure induced by myocardial infarction. The main finding of our study was that amlodipine, when administered for 10 weeks to rats after a myocardial infarction had been induced, had no significant effects on in vitro and in vivo hemodynamics or neurohormones. The effect of amlodipine on endothelium-intact, norepinephrine-precontracted aortic rings appears to differ from the placebo treatment with respect to the endothelium-dependent relaxation, whereas no differences are seen in endothelium-independent relaxation. We conclude that our data do not support a beneficial role of amlodipine on endothelial function in chronic heart failure.
de Vries
R J
RJ
Department of Cardiology, University Hospital Groningen, The Netherlands.
Anthonio
R
R
van Veldhuisen
D J
DJ
Scholtens
E
E
Buikema
H
H
van Gilst
W H
WH
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003327:Coronary Disease / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D006333:Heart Failure / Q000188:drug therapy*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D017311:Amlodipine; D009638:Norepinephrine