Restoration of erectile function by suppression of corporal apoptosis and oxidative stress with losartan in aged rats with erectile dysfunction.

BACKGROUND

The prevalence of erectile dysfunction (ED) increases progressively with age, but its potential pathophysiology has not been fully demonstrated. Hence, this article was aimed to identify the functional and morphological characterization of the corpus cavernosum in aged rats and to evaluate the effects of the Angiotensin II type 1 receptor antagonist losartan on age-related ED (AED).

MATERIAL AND

METHODS

A total of 40 young and aged Sprague Dawley rats were randomly divided into four groups (n = 10 per group): young rats as normal controls (YNC) group; aged rats with normal erectile function (ANC) group; aged rats with ED (AED) group; and a losartan-treated AED (AED + Losartan) group. The treated group received losartan (30 mg/kg) once daily oral gavage for 4 weeks. Erectile function was measured by the ratio of peak intracavernous pressure (ICP)/mean arterial pressure (MAP), and relevant tissues were harvested for transmission electron microscopy, Immunohistochemistry, Masson's trichrome staining, TUNEL, caspase-3 activity assay and Western blot.

RESULTS

The AED group exhibited decreases in erectile response and increases in the role of apoptosis, fibrosis as well as oxidative stress, compared with the control groups. After daily administration of losartan for four weeks, it could slightly restore erectile function and significantly attenuate corporal apoptosis, fibrosis, and oxidative stress of AED. However, the result was still not comparable with that of the control groups. Moreover, the expression levels of p-Bad/Bad and p-AKT/AKT were significantly lower, whereas the expression levels of Bax/Bcl-2, Nrf2/Keap-1, Fibronectin, HO-1, and caspase-3 activity were significantly higher in the AED groups and while losartan could significantly attenuate these changes of AED, it was still not comparable with that of the control groups.

CONCLUSIONS

Our results indicated that administration of losartan not merely restored erectile function, but also significantly prevented corporal apoptosis and oxidative stress in AED by suppressing the Akt/Bad/Bax/caspase-3 and Nrf2/Keap-1 pathways.