Background: High salt intake is a risk factor for hypertension, which can potentially lead to erectile dysfunction (ED); however, the underlying pathological mechanisms remain unclear. Aim: To investigate whether erectile function is directly impaired by high salt intake and whether selective inhibition of mineralocorticoid receptor (MR) could provide protection from ED. Methods: 6-week-old male Dahl salt-sensitive rats were randomly divided into 3 groups: normal diet (0.3% NaCl; control, n ¼ 8), high-salt diet (8% NaCl; HS, n ¼ 8), and high-salt diet plus eplerenone (HS þ EPL, n ¼ 11). HS þ EPL rats were orally administered daily doses of EPL (75 mg/kg) for 6 weeks; control and HS rats received purified water on the same schedule. Outcomes: At the end of the study period, erectile function was evaluated by measuring intracavernosal pressure and mean arterial pressure after cavernous nerve stimulation. Serum levels of asymmetric dimethylarginine and L-arginine were determined using ultraperformance liquid chromatographyetandem mass spectrometry. Quantitative PCR was used to assess the expression of MR, inflammation, and oxidative stress markers (nicotinamide adenine dinucleotide phosphate oxidase-1/4, p22 phox , interleukin-6, and superoxide dismutase-1), and protein arginine N-methyltransferase-1. Results: The intracavernosal pressure/mean arterial pressure ratio was significantly lower, whereas systolic blood pressure, MR expression, serum asymmetric dimethylarginine levels, oxidative stress, and levels of inflammatory biomarkers were significantly higher in HS rats than in control rats (P < .05). EPL administration significantly improved each of these parameters except systolic blood pressure and MR expression. No significant intergroup differences were observed for L-arginine and superoxide dismutase-1 levels. Clinical Translation: Our results provide a rationale for the need of salt restriction and the use of selective MR inhibitors in prophylaxis or treatment of ED in men consuming a high-salt diet. Strengths & Limitations: We are the first to report that the adverse impact of high salt intake on erectile function is mediated via MR activation, independent of its effect on blood pressure. A major limitation of this study is that responses of salt-resistant rats were not studied. Conclusions: High salt intake directly impaired erectile function in Dahl salt-sensitive rats, whereas selective MR inhibition ameliorated this effect. Kishimoto T, Kataoka T, Yamamoto Y, et al. High Salt Intake Impairs Erectile Function in Salt-Sensitive Rats Through Mineralocorticoid Receptor Pathway Beyond Its Effect on Blood Pressure.
Background: Because androgen replacement therapy (ART) is not performed immediately after the onset of androgen deficiency, the treatment is considered to be late. Aim: To investigate the effects of late ART, starting 4 weeks after castration of rats, on erectile function and structural changes in the corpus cavernosum. Methods: Rats were subjected to ART for 4 (Late-ART [4w]) or 8 (Late-ART [8w]) weeks. In either case, rats were assigned to the following groups: castrated (Cast), castrated with subcutaneous administration of testosterone (3 mg/kg/day; Cast+T), and sham (Sham). Cast + T rats received daily subcutaneous doses of testosterone starting 4 weeks after castration for 4 or 8 weeks whereas Sham and Cast rats received only the vehicle. Outcomes: Erectile function was assessed by evaluating intracavernosal pressure (ICP) and mean arterial pressure (MAP) after electrical stimulation of the cavernous nerve, corporal veno-occlusive function using dynamic infusion cavernosometry, and histology using Masson's trichrome staining. Results: No increase in the ICP was observed in Cast+T rats in the Late-ART (4w) group (0.47 § 0.02, P > .05), whereas, in Cast+T rats in the Late-ART (8w) group, there was a significant increase in the ICP/MAP ratio (0.60 § 0.02, P < .05), drop rate, and smooth muscle/collagen ratio. Clinical Translation: The present study provides scientific evidence for the effect of late ART on erectile function. Strengths and Limitations:This study provides insights into the influence of late ART on erectile function through improvements in the structure of corpus cavernosum. The major limitation of this study is the difference in the time required for healing between the humans and rats, which might have a bearing on the translational relevenace of the results. Conclusions: Late ART could improve erectile function. However, as improvement requires a considerable time period, it is necessary to persist with therapy patiently for optimal results. Kataoka T, Hotta Y, Yamamoto Y, et al. Effect of Late Androgen Replacement Therapy on Erectile Function Through Structural Changes in Castrated Rats. Sex Med 2021;XX:XX−XXX.
PurposeTo investigate whether relaxation of the rat penile corpus cavernosum could be controlled with NOBL-1, a novel, light-controllable nitric oxide (NO) releaser.Materials and MethodsFifteen-week-old male Wistar-ST rats were used. The penile corpus cavernosum was prepared and used in an isometric tension study. After noradrenaline (10-5 M) achieved precontraction, the penile corpus cavernosum was irradiated by light (470–500 nm) with and without NOBL-1 (10-6 M). In addition, we noted rats' responses to light with vardenafil (10-6 M), a phosphodiesterase-5 (PDE-5) inhibitor. Next, responses to light in the presence of a guanylate cyclase inhibitor, ODQ (1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one) (10-5 M), were measured. All measurements were performed in pretreated L-NAME (10-4 M) conditions to inhibit endogenous NO production.ResultsCorpus cavernosal smooth muscle, precontracted with noradrenaline, was unchanged by light irradiation in the absence of NOBL-1. However, in the presence of NOBL-1, corpus cavernosal smooth muscle, precontracted with noradrenaline, relaxed in response to light irradiation. After blue light irradiation ceased, tension returned. In addition, the light response was obviously enhanced in the presence of a PDE-5 inhibitor.ConclusionsThis study showed that rat corpus cavernosal smooth muscle relaxation can be light-controlled using NOBL-1, a novel, light sensitive NO releaser. Though further in vivo studies are needed to investigate possible usefulness, NOBL-1 may be prove to be a useful tool for erectile dysfunction therapy, specifically in the field of penile rehabilitation.
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