Abstract
Objective
To determine the effect of heart rate reduction with ivabradine on atherosclerotic
lesions and erectile dysfunction.
Methods
Two different treatment regimes with ivabradine were applied in wild-type (C57/B6)
and ApoE−/−-mice to study effects of ivabradine on erectile function and atherosclerosis in animals
with and without present endothelial dysfunction. Preventive effects of ivabradine
were evaluated in animals fed a high-cholesterol diet in parallel to treatment with
ivabradine (orally via chow, 10 mg/kg per day). The other treatment regime started treatment with a high-cholesterol
diet for 4 weeks to induce endothelial dysfunction. Thereafter, treatment with ivabradine
(orally via chow, 15 mg/kg per day) was started in ApoE−/− mice for 3 months. Vital parameters were measured using the tail-cuff method. Erectile
function was assessed by pharmacological stimulation of corpora cavernosa in organ
bath chambers. Atherosclerotic plaque formation, oxidative stress, eNOS and collagen
content were determined.
Results
Treatment with ivabradine significantly reduced heart rate (p < 0.01), with no effect on blood pressure. Aortic atherosclerotic lesion size decreased
with ivabradine in both treatment regimes (p < 0.05). Endothelium-dependent relaxation of corpora cavernosa significantly decreased
in ApoE−/−-mice with a restoration by ivabradine in prevention and reversal. Dihydroethidium-stained
penile sections (p < 0.05) and lipid peroxidase assay (p < 0.05) revealed a reduction in superoxide production in ivabradine-treated animals.
Penile eNOS-expression increased and collagen content significantly decreased (p < 0.01) in ivabradine-treated animals.
Conclusion
Ivabradine improves penile endothelial function by reduction of oxidative stress and
penile fibrosis. Beneficial effects were achieved in prevention and manifest endothelial
dysfunction.
Keywords
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Article info
Publication history
Published online: March 29, 2010
Accepted:
March 2,
2010
Received in revised form:
February 22,
2010
Received:
June 25,
2009
Identification
Copyright
© 2010 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
