The tACE/Angiotensin (1–7)/Mas Axis Protects Against Testicular Ischemia Reperfusion Injury

• Published in: Urology (Ridgewood, N.J.) N.J.), 2016-08, Vol.94, p.312.e1-312.e8
• Main Authors: Al-Maghrebi, May, Renno, Waleed M
• Format: Article
• Language: English
• Subjects: Angiotensin I - physiology; Angiotensin I - therapeutic use; Animals; Male; Peptide Fragments - physiology; Peptide Fragments - therapeutic use; Peptidyl-Dipeptidase A - biosynthesis; Peptidyl-Dipeptidase A - physiology; Proto-Oncogene Proteins - physiology; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled - physiology; Reperfusion Injury - etiology; Reperfusion Injury - prevention & control; Testis - blood supply; Testis - metabolism; Urology
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/j.urology.2016.04.021

Objective To investigate whether exogenous angiotensin (Ang)-(1-7) administration can protect against the damaging consequences of testicular ischemia reperfusion (tIR) injury. Materials and Methods Eighteen male Sprague-Dawley rats were divided equally among the following 3 groups: sham, unilateral tIR injury (1 hour of ischemic treatment and 4 hours of reperfusion), and tIR + Ang-(1-7) (0.3 mg/kg). Testicular tissues obtained from the rats were evaluated for the expression of testicular angiotensin-converting enzyme (tACE), Ang-(1-7), and the Ang-(1-7)-specific receptor Mas by immunohistochemistry and enzyme-linked immunosorbent assay. Reduced spermatogenesis, induction of the caspase-8 pathway, and nitric oxide (NO) generation were assessed. The effects of tIR and Ang-(1-7) treatment on the PI3K/Akt antiapoptosis pathway were also investigated. Results Testicular morphological changes and reduced spermatogenesis associated with decreased expression of the tACE/Ang-(1-7)/Mas axis were observed during tIR. These effects were also accompanied by increased activity of caspase-3 and -8, downregulation of the survivin and BAD transcripts, and decreased NO formation. During tIR, PTEN expression was increased, leading to inactivation of the PI3K/Akt pathway. Acute treatment with Ang-(1-7) prior to reperfusion attenuated the tIR-induced damage described above. Conclusion Expression of the tACE/Ang-(1-7)/Mas axis was downregulated during tIR. Administration of exogenous Ang-(1-7) prior to reperfusion rescued tACE and Mas expression and protected against germ cell apoptosis and oxidative stress. Increased NO generation and activation of the PI3K/Akt signaling pathway may have partially contributed to these effects. The tACE/Ang-(1-7)/Mas axis likely plays a role in the maintenance of normal testis physiology and spermatogenesis.