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Nitric oxide mediated effects of nebivolol on erectile function in rats with heart failure

  • Guldem Mercanoglu1
  • Gulistan Gumrukcu2
  • Caglar Macit3

1Department of Pharmacology, Hamidiye Pharmacy Faculty, University of Health Sciences, 34668 Istanbul, Turkey

2Department of Pathology, Haydarpasa Numune Training and Research Hospital, University of Health Sciences, 34668 Istanbul, Turkey

3Department of Pharmacology, School of Pharmacy, Istanbul Medipol University, 34815 Istanbul, Turkey

DOI: 10.31083/jomh.2021.071

Submitted: 09 February 2021 Accepted: 19 March 2021

Online publish date: 14 July 2021

*Corresponding Author(s): Guldem Mercanoglu E-mail:

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Background and objective: Heart failure (HF) is a common complication of cardiovascular disease, which leads to functional cardiac abnormalities. Beta-blockers are commonly used to reduce mortality in HF patients; however, they are associated with an increased risk of erectile dysfunction (ED). Nebivolol is a third-generation beta-blocker with also having a Nitric oxide (NO) releasing effect. NO plays a key role in penile erection. The aim of this study was to investigate the NO-mediated effects of nebivolol on ED in HF.

Material and methods: Twenty-four weeks old rats were divided into three groups: sham-operated control (SC), HF-induced control (HFC), and nebivolol-treated (HFNEB). HF was induced by the ligation of the left anterior descending coronary artery. Eight weeks after the ligation, functional, hemodynamic, biologic, and histologic studies were conducted to assess NO-mediated effects of nebivolol.

Results: HF rats displayed impaired erectile function represented by decreased intracavernosal/mean arterial pressure ratio (ICP/MAP). Increased nitrosative damage/decreased antioxidant capacity was consistent with decreased endothelial NOS (eNOS) and increased inducible NOS (iNOS) and neuronal NOS (nNOS) immunoreactivity in this group. Nebivolol treated animals were characterized by improved functional capacity, increased antioxidant and decreased oxidant capacity. Prevention of eNOS and an increase in nNOS immunoreactivity was also significant in this group.

Conclusion: Our study showed the positive effects of nebivolol on erectile function in HF. NO-mediated mechanisms behind this effect can be summarized as eNOS mediated dilation of the cavernous body and nNOS mediated smooth muscle relaxation. To the best of our knowledge, this study is the first in the literature to discuss all three NOS isoforms in order to explain the NO-mediated effects of nebivolol in ED.


Erectile dysfunction; Nitric oxide; Heart failure; Nitric oxide synthase; Nebivolol

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Guldem Mercanoglu,Gulistan Gumrukcu,Caglar Macit. Nitric oxide mediated effects of nebivolol on erectile function in rats with heart failure. Journal of Men's Health. 2021.doi:10.31083/jomh.2021.071.


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