Presentation Authors: Esther GarcÃa Rojo*, Javier Angulo, Borja GarcÃa GÃ³mez, Juan Justo Quintas, RocÃo Santos PÃ©rez de la Blanca, JosÃ© Medina Polo, Javier Romero-Otero, Madrid, Spain
Introduction: The contribution of calcium Orai channels to contractile responses in human corpus cavernosum and penile arteries has been proposed, especially in pathological conditions such as erectile dysfunction (ED). The aim of the present work was to evaluate the influence of aging on Orai channels contribution to cavernosal tissue contraction.
Methods: The effect of the Orai channel inhibitor, YM-58483 (YM) was evaluated on contractions induced by norepinephrine (NE) in corpus cavernosum (CC) from young (3 months-old) and aged (20 months-old) rats. The effects of YM on endothelial relaxation and neurogenic contraction were also evaluated in tissues from aged rats. As well, the influence of YM on NE-induced contractions was determined in human corpus cavernosum (HCC) from organ donors (OD) without history of ED, which were divided into younger than 65 years (43.5Ã‚Â±2.8 years, n=16) and older than 65 years (74.2Ã‚Â±3.5 years, n=5). The expression of Orai channels in these HCCs was determined by Western blot.
Results: NE-induced contractions in CC from young rats were not significantly modified by YM (20 Ã‚ÂµM) (133.1Ã‚Â±3.1% vs. 127.9Ã‚Â±10.2% of K+-induced contraction, respectively). In contrast, the significantly increased NE-induced contractions in aged rats were clearly inhibited by YM (252.4Ã‚Â±22.5% vs.171.9Ã‚Â±7.2%, p < 0.01). YM significantly reduced neurogenic contractions and improved endothelial relaxations in CC from aged rats. In HCC, NE-induced contractions were significantly enhanced in old subjects (176.7Ã‚Â±17.5% vs. 130.9Ã‚Â±9.4%, p < 0.05). The treatment with YM only reduced contractile responses in HCC from old subjects, yielding similar contractions to those exhibited by younger subjects (103.8Ã‚Â±11.6% in younger vs. 108.1Ã‚Â±10.6% in older). Orai3 channel subtype was significantly overexpressed in HCC from older subjects.
Conclusions: Contribution of Orai channels to contractile tone in cavernosal tissue increases with aging and is paralleled by an increased expression of Orai3 channel. These results highlight the potential role of Orai channels as a therapeutic target in ED.