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Effects of amlodipine on endothelial function in rats with chronic heart failure after experimental myocardial
R J de Vries1, R Anthonio, D J van Veldhuisen
1Department of Cardiology, University Hospital Groningen, The Netherlands.
Insights
Amlodipine did not significantly improve endothelial function in rats with chronic heart failure. This study suggests amlodipine does not offer benefits for endothelial function in heart failure patients.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Endothelial Function
Background:
- Endothelial dysfunction is implicated in chronic heart failure, but its precise role remains unclear.
- Calcium channel blockers (CCBs) affect endothelial function, yet their use in heart failure is controversial due to potential negative inotropic effects and neurohormonal activation.
- Recent findings suggest amlodipine may improve mortality in heart failure patients, but the underlying mechanisms are unknown.
Purpose of the Study:
- To investigate the effect of amlodipine on endothelial function in a rat model of chronic heart failure.
- To determine if 10 weeks of amlodipine treatment influences in vitro and in vivo hemodynamics and neurohormonal markers in heart failure rats.
Main Methods:
- Congestive heart failure was induced in rats via myocardial infarction.
- Rats received either amlodipine or placebo treatment for 10 weeks.
- Endothelial function was assessed using in vitro (aortic ring relaxation) and in vivo hemodynamic measurements.
Main Results:
- Amlodipine treatment did not significantly alter in vitro or in vivo hemodynamics or neurohormone levels.
- Endothelium-dependent relaxation in norepinephrine-precontracted aortic rings showed a difference between amlodipine and placebo groups.
- No significant differences were observed in endothelium-independent relaxation between the groups.
Conclusions:
- The study's findings do not support a beneficial role for amlodipine in improving endothelial function in chronic heart failure.
- The observed difference in endothelium-dependent relaxation warrants further investigation but did not translate to overall hemodynamic improvement.
Abstract:
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.