Acute dual therapeutic effects of the BKCa channel opener LDD175 on erectile dysfunction and lower urinary tract symptoms in chronic pelvic ischemia: a preliminary study.
- Author:
Jiwoong YU
1
;
Mee Ree CHAE
;
Deok Hyun HAN
;
Su Jeong KANG
;
Jimin SHIN
;
Hyun Hwan SUNG
Author Information
- Publication Type:Journal Article
- Keywords: BKCa channel; LDD175; erectile dysfunction; lower urinary tract symptom
- MeSH: Male; Animals; Erectile Dysfunction/etiology*; Rats, Sprague-Dawley; Lower Urinary Tract Symptoms/etiology*; Ischemia/drug therapy*; Rats; Tamsulosin; Hypoxia-Inducible Factor 1, alpha Subunit/drug effects*; Sildenafil Citrate/therapeutic use*; Penis/blood supply*; Disease Models, Animal; Transforming Growth Factor beta1/metabolism*; Pelvis/blood supply*; Prostate/metabolism*; Sulfonamides/therapeutic use*; Large-Conductance Calcium-Activated Potassium Channels/agonists*
- From: Asian Journal of Andrology 2025;27(6):714-722
- CountryChina
- Language:English
- Abstract: Recent studies have revealed a significant relationship between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS), both of which commonly affect middle-aged and older men. These conditions share underlying causes, particularly endothelial dysfunction, atherosclerosis, and chronic pelvic ischemia (CPI). This study investigated the therapeutic potential of LDD175, a large-conductance Ca 2+ -activated K + channel (BKCa channel) opener, in simultaneously treating both conditions using a CPI animal model of male Sprague Dawley rats. Our study investigated the induction of CPI through surgical endothelial damage combined with a high-cholesterol diet. We assessed erectile and voiding functions by measuring intracavernosal pressure (ICP) and intraurethral pressure (IUP), respectively, after nerve stimulation. We performed histological examinations of vascular changes and western blot analyses of cavernous and prostate tissues to understand the underlying mechanisms. This study evaluated the effectiveness of LDD175 compared to standard treatments, such as sildenafil for ED and tamsulosin for LUTS. Therefore, the CPI model successfully demonstrated ED and LUTS symptoms with decreased ICP and increased IUP. Analysis revealed elevated levels of hypoxia-inducible factor-1α, transforming growth factor-β1 and β2 in cavernous tissue, and increased α1A-adrenoceptor expression in prostate tissue. LDD175 administration showed promising results, with dose-dependent improvements in ICP and IUP, and therapeutic effects comparable to those of established treatments. Our findings suggest a novel therapeutic approach that can simultaneously address ED and LUTS, opening new possibilities for clinical application in the treatment of these interconnected conditions.
