Chronic ethanol consumption induces erectile dysfunction: Role of oxidative stress

Muniz, Jaqueline Jóice; Leite, Letícia Nogueira; Martinis, Bruno Spinosa De; Carneiro, Fernando S.; Tirapelli, Carlos Renato

doi:10.1016/j.lfs.2015.09.017

Cited by 24 publications

(24 citation statements)

References 44 publications

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“…Much of neuronal and endothelial damage has been attributed to oxidative stress (Jeremy et al ., ). Several previous studies have indicated an important role for reactive oxygen species (ROS) in the pathogenesis of ED, through the overproduction of superoxide, resulting in the acute impairment of penile relaxation and long‐term vasculopathy of corpus cavernosum (Jeremy et al ., ; Kassan et al ., ; Muniz et al ., ). Corporal apoptosis resulting from oxidative stress in penile tissues was a major cause of erectile impairment (Ha et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function through increased endothelial dysfunction, oxidative stress, apoptosis, and corporal fibrosis in a rat model

Niu

Wang

et al. 2016

Andrology

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Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an independent risk factor for the development of erectile dysfunction (ED). But the molecular mechanisms underlying the relationship between CP/CPPS and ED are still unclear. The aim of this study was to investigate the effect of CP/CPPS on erectile function in a rat model and the possible mechanisms. A rat model of experimental autoimmune prostatitis (EAP) was established to mimic human CP⁄CPPS. Then twenty 2-month-old male Sprague-Dawley rats were divided into EAP group and control group. Intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured during cavernous nerve electrostimulation, the ratio of max ICP/MAP was calculated. Blood was collected to measure the levels of serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and testosterone, respectively. The expression of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in corpus cavernosum were detected. We also evaluated the smooth muscle/collagen ratio and apoptotic index (AI). The ratio of max ICP/MAP in EAP group were significantly lower than that in control group. The levels of serum CRP, TNF-α, IL-1β, and IL-6 in EAP group were all significantly higher than these in control group. The expression of eNOS and cGMP levels in corpus cavernosum of EAP rats were significantly downregulated. Furthermore, decreased SOD activity and smooth muscle/collagen ratio, increased MDA levels and AI were found in corpus cavernosum of EAP rats. In conclusion, CP/CPPS impaired penile erectile function in a rat model. The declines of eNOS expression and cGMP levels in corpus cavernosum may be an important mechanism of CP/CPPS-induced ED. CP/CPPS also increased oxidative stress, cell apoptosis and decreased smooth muscle/collagen ratio in corpus cavernosum of rats, which were all important for erectile function.

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Section: Discussionmentioning

confidence: 97%

Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function through increased endothelial dysfunction, oxidative stress, apoptosis, and corporal fibrosis in a rat model

Niu

Wang

et al. 2016

Andrology

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“…An attenuation of the contraction responses to Big ET‐1 was also observed in human vaginal smooth muscle after exposure of the tissue to KC 12615 (Rahardjo et al., ). ET‐1 has been reported to contribute to enhanced vasoconstriction in penile tissues obtained from subjects with an impairment in erectile response (Alkan et al., ; Muniz, Leite, De Martinis, Carneiro, & Tirapelli, ; Sánchez et al., ). Inhibition of endopeptidase activity, that catalyses the transformation of Big ET‐1 to ET‐1, has been suggested to counteract the Big ET‐1/ET‐1 axis, thus resulting in relaxation of vascular and nonvascular CC smooth muscle, an essential event in the normal male erectile process.…”

Section: Discussionmentioning

confidence: 99%

Endopeptidase inhibition attenuates the contraction induced by big endothelin‐1 of isolated human penile erectile tissue

et al. 2018

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Peptides, such as C-type natriuretic peptide (CNP), vasoactive intestinal polypeptide (VIP) and endothelin 1 (ET-1), are involved in the control of penile erectile tissue (corpus cavernosum = CC). Inhibiting the degradation of CNP and VIP or conversion of Big ET-1 into ET-1 by endopeptidase enzymes should result in an enhancement of CC smooth muscle relaxation. Using the tissue bath technique, responses of isolated CC, challenged by noradrenaline (NA, 1 μm), to increasing concentrations of the endopeptidase inhibitor KC 12615 (1 nm - 10 μm), CNP and VIP (0.1 nm - 1 μm), were investigated. Effects of CNP, VIP and Big ET-1 (0.1 nm - 100 nm) on the tissue tension were also evaluated following pre-exposure to 10 μm of KC 12615. Big ET-1 induced contraction of the CC amounting to a force generation of 1,200 mg. The contraction was attenuated in the presence of KC 12615 by 35% and 50%, respectively. The tension induced by NA was reversed by VIP and CNP to 38.7% ± 15.8% and 61% ± 13%, respectively, of the initial force. The findings might be of significance with regard to future pharmacological treatment options for male ED, where an endothelial dysfunction exists.

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“…Several studies have established a positive relationship between ED and ethanol consumption (Grinshpoon et al 2007;Ponizovsky 2008), but the mechanisms underlying ethanol-induced ED are not fully understood. Recently, we provided evidence that chronic ethanol consumption decreased intracavernosal pressure in rats (Muniz et al 2015a). This response was accompanied by increased levels of circulating endothelin (ET)-1, increased generation of reactive oxygen species (ROS) and increased expression of ET-1 and ET A receptors in the rat cavernosal smooth muscle (CSM) (Muniz et al 2015a;Leite et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Dysregulated mitogen-activated protein kinase and matrix metalloproteinase in ethanol-induced cavernosal dysfunction

Muniz

Leite

Lacchini

et al. 2018

Can. J. Physiol. Pharmacol.

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We evaluated the effects of ethanol consumption on the mitogen-activated protein kinases (MAPK) and metalloproteinases (MMP) pathways in the rat cavernosal smooth muscle (CSM). Male Wistar rats were treated with ethanol (20% v/v) for 6 weeks. Quantitative real-time polymerase chain reaction experiments showed that ethanol consumption did not alter mRNA levels of p38MAPK, SAPK/JNK, ERK1/2, MMP-2, or MMP-9 in the rat CSM. Western immunoblotting experiments revealed decreased protein expression of p38MAPK and phosphorylation of SAPK/JNK in the CSM from ethanol-treated rats. Additionally, ethanol consumption decreased the expression of MMP-2. Functional assays showed that SP600125, an inhibitor of SAPK/JNK, prevented the increase in endothelin (ET)-1-induced contraction in the CSM from ethanol-treated rats. Treatment with ethanol decreased MMP-2 activity, but did not change net MMP activity in the rat CSM. Ethanol consumption increased the circulating levels of MMP-2, MMP-9, and TIMP-2 as well as the MMP-9/TIMP-1 ratio. The major finding of our study is that ethanol consumption down-regulates both MAPK and MMP pathways in the rat CSM, whereas it increases the circulating levels of MMP-9. Additionally, we found that SAPK/JNK plays a role in ethanol-induced increase on ET-1 contraction in the isolated rat CSM.

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Chronic ethanol consumption induces erectile dysfunction: Role of oxidative stress

Cited by 24 publications

References 44 publications

Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function through increased endothelial dysfunction, oxidative stress, apoptosis, and corporal fibrosis in a rat model

Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function through increased endothelial dysfunction, oxidative stress, apoptosis, and corporal fibrosis in a rat model

Endopeptidase inhibition attenuates the contraction induced by big endothelin‐1 of isolated human penile erectile tissue

Dysregulated mitogen-activated protein kinase and matrix metalloproteinase in ethanol-induced cavernosal dysfunction

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