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 ...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 Ca2+-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 andβ2 in cavernous tissue,and increasedα1A-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.展开更多
In this study, we investigated the effects of a combination of Ginkgo biloba extracts （GBE） and phosphodiesterase type 5 （PDE-5） inhibitors on the muscular tone of the corpus cavernosum and potassium channel activ...In this study, we investigated the effects of a combination of Ginkgo biloba extracts （GBE） and phosphodiesterase type 5 （PDE-5） inhibitors on the muscular tone of the corpus cavernosum and potassium channel activity of corporal smooth muscle cells. Strips of corpus cavernosum from male New Zealand white rabbits were mounted in organ baths for isometric tension studies. After contraction with 1 × 10^-5 mol I^-1 norepinephrine, GBE （0.01-1 mg ml^-1） and mirodenafil （0.01-100 nmol I^-1） were added together into the organ bath. In electrophysiological studies, whole-cell currents were recorded by the conventional patch-clamp technique in cultured smooth muscle cells of the human corpus cavernosum. The corpus cavemosum was relaxed in response to GBE in a dose-dependent manner （from 0.64%±8.35% at 0.01 mg ml^-1 to 52.28%±11.42% at 1 mg ml^-1）. After pre-treatment with 0.03 mg ml^-1 of GBE, the relaxant effects of mirodenafil were increased at all concentrations, After tetraethylammonium （TEA） （1 mmol I^-1） administration, the increased effects were inhibited （P〈0.01）. Extracellular administration of GBE increased the whole-cell K^＋ outward currents in a dose-dependent fashion. The increase of the outward current was inhibited by I mmol 1-1 TEA. These results suggest that GBE could increase the relaxant potency of mirodenafil even at a minimally effective dose. The K＋ flow through potassium channels might be one of the mechanisms involved in this synergistic relaxation.展开更多
文摘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 Ca2+-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 andβ2 in cavernous tissue,and increasedα1A-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.
文摘In this study, we investigated the effects of a combination of Ginkgo biloba extracts （GBE） and phosphodiesterase type 5 （PDE-5） inhibitors on the muscular tone of the corpus cavernosum and potassium channel activity of corporal smooth muscle cells. Strips of corpus cavernosum from male New Zealand white rabbits were mounted in organ baths for isometric tension studies. After contraction with 1 × 10^-5 mol I^-1 norepinephrine, GBE （0.01-1 mg ml^-1） and mirodenafil （0.01-100 nmol I^-1） were added together into the organ bath. In electrophysiological studies, whole-cell currents were recorded by the conventional patch-clamp technique in cultured smooth muscle cells of the human corpus cavernosum. The corpus cavemosum was relaxed in response to GBE in a dose-dependent manner （from 0.64%±8.35% at 0.01 mg ml^-1 to 52.28%±11.42% at 1 mg ml^-1）. After pre-treatment with 0.03 mg ml^-1 of GBE, the relaxant effects of mirodenafil were increased at all concentrations, After tetraethylammonium （TEA） （1 mmol I^-1） administration, the increased effects were inhibited （P〈0.01）. Extracellular administration of GBE increased the whole-cell K^＋ outward currents in a dose-dependent fashion. The increase of the outward current was inhibited by I mmol 1-1 TEA. These results suggest that GBE could increase the relaxant potency of mirodenafil even at a minimally effective dose. The K＋ flow through potassium channels might be one of the mechanisms involved in this synergistic relaxation.
