The potential effect of ambrisentan as monotherapy and combined with tadalafil on diabetic erectile dysfunction in rats

• Published in: Urologia Vol. 91; no. 1; pp. 159 - 169
• Main Authors: Azmy Nabeh, Omnia, Ahmed El-Batrawy, Fatma, Anwar Khorshid, Omayma, Farouk Soliman, Ghada
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-02-2024
• Subjects: diabetic; endothelin; tadalafil; Ambrisentan; erectile dysfunction
• ISSN: 0391-5603; 1724-6075
• DOI: 10.1177/03915603231192737

Introduction:
This study investigated the role of ambrisentan; the selective endothelin type-A receptor (ETAR) blocker on experimental diabetic erectile dysfunction in rats.
Materials and methods:
Eighty-four adult male Sprague Albino rats were divided randomly into 7 groups. Three control groups received 1 mL saline, 0.2 mg/kg/d ambrisentan and 1.5 mg/kg/d tadalafil, respectively orally for 4 weeks. The remaining four groups were fed high fat diet for 14 days. Diabetes was induced by a single intra-peritoneal injection of 40 mg/kg streptozotocin. After 72 h, diabetes was confirmed by plasma glucose level ⩾250 mg/dL. Diabetic rats were divided randomly into four groups, numbered from 4 to 7. The fourth group was the diabetic-control group, while the fifth and sixth groups received ambrisentan and tadalafil respectively. The seventh group received a combination of both drugs. Treatment continued for 4 weeks then, copulatory, intracavernous pressure measurement, and laboratory tests were conducted.
Results:
In diabetic rats, ambrisentan and tadalafil improved fasting glucose, insulin, insulin resistance, testosterone, nitric oxide, and rho kinase (ROCK) values compared to diabetic group with the maximum improvement achieved in ambrisentan/tadalafil group (p < 0.05). Ambrisentan also enhanced ICP and improved latency to erection and number of mounts with a tolerable SBP. Yet, ambrisentan/tadalafil combined therapy resulted in deterioration in SBP with consecutive worsening in ICP and mating indices.
Conclusion:
Ambrisentan showed significant therapeutic potential to prevent and improve diabetic ED in rats comparable to tadalafil.