Effect of BKCa Channel Opener LDD175 on Erectile Function in an In Vivo Diabetic Rat Model

Sung, Hyun Hwan; Kang, Su Jeong; Chae, Mee Ree; Kim, Hye Kyung; Park, Jong Kwan; Kim, Chul Young; Lee, Sung Won

doi:10.1016/j.jsxm.2016.11.316

Cited by 9 publications

(6 citation statements)

References 24 publications

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“…[29,30]. The SHR-S1.5 group presented an improved erectile function, corroborating with reports in the literature [31][32][33]. Interestingly, no differences were observed in terms of the erectile function of the SHR-C100…”

Section: Discussionsupporting

confidence: 89%

Carvacrol Improves Erectile Dysfunction in Spontaneously Hypertensive Rats

Gonçalves¹,

Maciel²,

Villanueva³

et al. 2019

Preprint

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Carvacrol is a monoterpene found in essential oils from various plants. Several pharmacological properties have already been described for carvacrol, including antimicrobial, anti-inflammatory, anticarcinogenic, antioxidant, vasorelaxant and hypotensive activities. The present study evaluated the effect of carvacrol on hypertensive rats with erectile dysfunction. Twelve-week-old spontaneously hypertensive rats (SHR) were treated with vehicle, carvacrol (50 or 100 mg/kg/day) or sildenafil (1.5 mg/kg/day), intragastrically, for four weeks. Wistar Kyoto (WKY) rats were used as the normotensive controls. All substances tested reduced systolic blood pressure during the treatment period. The intracavernosal pressure/mean arterial pressure ratio of the hypertensive rats was improved by carvacrol and sildenafil treatments. In isolated rat corpora cavernosa, the acetylcholine- and SNP-induced relaxation responses were significantly increased by carvacrol or sildenafil treatments. In SHR corpora cavernosa, treatment with carvacrol attenuated the hypercontractility induced by phenylephrine or electrical field stimulation. Phe-induced hypercontractility in the presence of tempol was not altered when compared to the response induced by carvacrol alone. In rat corpora cavernosa fluorescence intensity emitted by the DHE probe was significantly reduced in SHR treated (carvacrol or sildenafil) groups when compared to that emitted in the SHR-CTL. This study showed that carvacrol improves the erectile function of hypertensive rats and reduces endothelial dysfunction, smooth muscle cell hypercontractility and superoxide anion generation.

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Section: Discussionsupporting

confidence: 89%

Carvacrol Improves Erectile Dysfunction in Spontaneously Hypertensive Rats

Gonçalves¹,

Maciel²,

Villanueva³

et al. 2019

Preprint

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“…The results obtained by Sung and colleagues showed that another activator of these channels, LDD175, improved erectile function in a diabetic rat model. Furthermore, they showed that LDD175 treatment combined with sildenafil had an additive effect on improving the erectile function of diabetic rats (Nilius and Owsianik, 2011;Sung et al, 2017). These findings suggest that BK Ca channels are possible targets for the treatment of ED.…”

Section: Ion Channels and Erectile Dysfunctionmentioning

confidence: 95%

Ionic Channels as Potential Therapeutic Targets for Erectile Dysfunction: A Review

et al. 2020

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Erectile dysfunction (ED) is a prevalent condition, especially in men over 40 years old, characterized by the inability to obtain and/or maintain penile erection sufficient for satisfactory sexual intercourse. Several psychological and/or organic factors are involved in the etiopathogenesis of ED. In this context, we gathered evidence of the involvement of Largeconductance, Ca 2+-activated K + channels (BK Ca), Small-conductance, Ca 2+-activated K + channels (SK Ca), KCNQ-encoded voltage-dependent K + channels (K V 7), Transient Receptor Potential channels (TRP), and Calcium-activated Chloride channels (CaCC) dysfunctions on ED. In addition, the use of modulating agents of these channels are involved in relaxation of the cavernous smooth muscle cell and, consequent penile erection, suggesting that these channels are promising therapeutic targets for the treatment of erectile dysfunction.

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“…In vivo cavernous nerve stimulation was performed to investigate erectile function. The detailed methodology for measuring the erectile response to cavernous nerve stimulation has been described in previous studies [15]. The electrical field stimulation (EFS) parameters were as follows: 1, 2.5, and 5 V, 5 ms, 2 Hz, and a duration of 60 s using an electric stimulator (model PG 721A; Austin Electronic Specialties, Inc., Palo Alto, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…The electrical field stimulation (EFS) parameters were as follows: 1, 2.5, and 5 V, 5 ms, 2 Hz, and a duration of 60 s using an electric stimulator (model PG 721A; Austin Electronic Specialties, Inc., Palo Alto, CA, USA). Sub-maximal EFS was introduced with 1 and 2.5 V as previously described [15]. By subdividing the power of stimulation, the subtle effects of erection could be compared among the groups.…”

Section: Methodsmentioning

confidence: 99%

Persistent Erectile Dysfunction after Discontinuation of 5-Alpha Reductase Inhibitor Therapy in Rats Depending on the Duration of Treatment

Sung

Kang

et al. 2019

World J Mens Health

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Purpose The current study is aimed to assess whether a longer duration of 5α-reductase inhibitor (5α-RI) exposure was associated with higher rate of permanent erectile dysfunction (ED) in a rat model. Materials and Methods Male Sprague-Dawley rats (n=76) were assigned to five groups: (i) normal control group; (ii) dutasteride (0.5 mg/rat/d) for 4-weeks group; (iii) dutasteride for 4-weeks plus 2-weeks of resting group; (iv) dutasteride for 8-weeks group; and (v) dutasteride for 8-weeks plus 2-weeks of resting group. In vivo erectile responses to electrical stimulation, and changes of fibrotic factors and smooth muscle/collagen contents in the corpus cavernosum were evaluated in each group. Results Dutasteride administration for 4 and 8 weeks significantly decreased erectile parameters compared with the control group. Reduced erectile responses were recovered during 2 weeks of drug-free time in the 4-week treatment group, but were not in the 8-week group. Protein levels of fibrosis-related factors transforming growth factor (TGF)-β1, TGF-β2, and p-Smad/Smad (Smad 2/3) in the corpus cavernosum showed no significant change after 4 weeks of dutasteride oral administration, but were enhanced after 8 weeks. Dutasteride markedly decreased smooth muscle content and increased collagen after 4 and 8 weeks of use, but no nuclear size changes; however, neither group showed significant improvement in the smooth muscle to collagen ratio after the rest period. Conclusions Our study showed that recovery from ED depended on the duration of medication, and administration of dutasteride for more than 8-weeks in rats could result in irreversible ED even after discontinuation of medication.

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Effect of BKCa Channel Opener LDD175 on Erectile Function in an In Vivo Diabetic Rat Model

Cited by 9 publications

References 24 publications

Carvacrol Improves Erectile Dysfunction in Spontaneously Hypertensive Rats

Carvacrol Improves Erectile Dysfunction in Spontaneously Hypertensive Rats

Ionic Channels as Potential Therapeutic Targets for Erectile Dysfunction: A Review

Persistent Erectile Dysfunction after Discontinuation of 5-Alpha Reductase Inhibitor Therapy in Rats Depending on the Duration of Treatment

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