PS-04-009 Investigation for Testosterone Deficiency on Erectile Function Through Asymmetric Dimethylarginine (ADMA) Pathway in Castrated Rats

Testosterone mediates the penile erectile response by maintaining an adequate supply of nitric oxide (NO); hence, testosterone deficiency leads to erectile dysfunction via reduced NO bioavailability. However, the mechanisms underlying endothelial dysfunction in testosterone-deficient males remain unclear. We investigated the mechanism underlying endothelial dysfunction, including the asymmetric dimethylarginine (ADMA) pathway, in a rat model of testosterone deficiency. Rats were assigned to the castrated (Cast), castrated with testosterone (Cast+T), or sham (Sham) groups. In the Cast+T group, castrated rats were treated daily with subcutaneous testosterone (3 mg/kg/day) for 4 weeks; the Sham and Cast rats received only the vehicle. Erectile function was assessed using intracavernosal pressure (ICP) and mean arterial pressure (MAP) measurements, after electrical stimulation of the cavernous nerve. Levels of ADMA—an endogenous NOS inhibitor—were measured using ultra-performance liquid chromatography–tandem mass spectrometry. Inflammatory and ADMA metabolic biomarker expressions were examined with the polymerase chain reaction. The ICP/MAP ratios were 0.61 ± 0.03, 0.26 ± 0.04, and 0.56 ± 0.06 in the Sham, Cast (p < 0.01 vs Sham), and Cast+T (p < 0.01 vs Cast) groups, respectively. mRNA expression levels of NADPH oxidase and p22phox (oxidative stress markers) as well as iNOS, IL-6, and NF-κB (inflammation markers) were significantly higher in the Cast than in the Sham and Cast+T groups (p < 0.05). The serum ADMA levels were significantly higher in the Cast than in the Sham and Cast+T groups (p < 0.05). The expression of PRMT-1 (marker of ADMA production) was significantly higher in the Cast than in the Sham or Cast+T groups (both p < 0.01).