High Salt Intake Impairs Erectile Function in Salt-Sensitive Rats Through Mineralocorticoid Receptor Pathway Beyond Its Effect on Blood Pressure

Abstract

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.

Oxaliplatin, an Anticancer Agent, Causes Erectile Dysfunction in Rats due to Endothelial Dysfunction

“…Blood pressure and heart ratio were measured as per methods previously reported. 11,12 Systemic and diastolic arterial blood pressure of the rats were measured before and after treatment, using a noninvasive automatic device (BP-98A-L, Softron, Tokyo, Japan). Mean arterial pressure was automatically calculated by the device.…”

“…qRT-PCR analysis was performed as previously reported. 11,13 Total RNA was extracted from CC samples (n = 6) after ICP measurement using ISOGEN (Nippon Gene, Tokyo, Japan) according to the manufacturer's instructions. Using a ReverTra Ace-a kit (Toyobo, Osaka, Japan), 1 mg of total RNA was reverse-transcribed into complementary DNA, which served as the template for qRT-PCR performed using the Power SYBR PCR Master Mix (Applied Biosystems, Tokyo, Japan).…”

Evaluating the Effects of Low Carbohydrate and High Protein Diet on Erectile Function in Rats

“…Blood pressure was measured as per methods previously reported. 9 , 10 Systemic and diastolic arterial blood pressures of the rats were measured at 0, 2, and 4 weeks, using a noninvasive automatic device (BP-98A-L, Softron, Tokyo, Japan). Mean arterial pressure was automatically calculated by the device.…”

“…Intracavernous pressure (ICP) was measured by electrical stimulation as previously reported. 9 , 10 , 11 , 12 , 13 Briefly, rats from each group (n = 8) were anaesthetized with isoflurane using inhalation anesthesia apparatus. The carotid artery was cannulated for continuous monitoring of the mean arterial pressure (MAP) and the left crus of the CC was cannulated using a 23-G needle for continuous ICP monitoring.…”

Gosha-Jinki-Gan Improved Erectile Dysfunction Caused by Anti-Cancer Agent Oxaliplatin by Decreasing Transcriptional Expression of Phosphodiesterase-5 in Rats

“…Real-time quantitative polymerase chain reaction (qRT-PCR) analysis was performed as previously reported. 10 , 13 , 17 Total RNA was extracted from corpus cavernosum samples using TriPure Isolation Reagent (Sigma-Aldrich, St. Louis, MO, USA) according to the manufacturer's instructions. Using a ReverTra Ace-α kit (Toyobo, Osaka, Japan), 1 µg of total RNA was reverse-transcribed into complementary DNA, which served as the template for qRT-PCR performed using the KAPA SYBR Fast qPCR Kit (Roche, Pleasanton, CA, USA).…”