Implication of Rho‐kinase and soluble guanylyl cyclase enzymes in prostate smooth muscle dysfunction in middle‐aged rats

Calmasini, Fabiano Beraldi; Silva, Fábio H.; Alexandre, Eduardo C.; Rodrigues, Renata Lopes; Barbosa, Ana Paula L.; Ferrucci, Danilo Lopes; Carvalho, Hernandes F.; Anhê, Gabriel Forato; Pupo, André S.; Antunes, Edson

doi:10.1002/nau.22990

Cited by 8 publications

(6 citation statements)

References 31 publications

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“…Few studies in the literature have addressed prostate smooth muscle contractility in 6 to 10-month-old rats. According to the published data, 10-month-old rats exhibited EFS-and phenylephrine-induced prostate smooth muscle hypercontractility (Calmasini et al, 2016), which are of the same magnitude as in the 8-month-old rats presented here. This is a valuable finding, suggesting that increased prostate smooth muscle contractility achieves a plateau in 8-month-old rats.…”

Section: Discussionsupporting

confidence: 83%

“…Besides the adrenergic pathway, it is well characterized that human and rodent prostates are also innerved by cholinergic and non-adrenergic noncholinergic neurons (Michel, Vrydag, 2006), which are altered during the aging process. For instance, 10-month-old rats exhibited increased prostate smooth muscle contractility to the purinergic agonist alpha, beta-methylene ATP and reduced isoproterenol (a betaadrenoceptor agonist)-induced prostate smooth muscle relaxation (Calmasini et al, 2016). In aged mice, increased PSM contraction induced by purinoceptor activation was associated with reduced ATP breakdown in the prostate (White et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…2022;58: e21063 Tabatha Danielle da Silva Lopes, Renan Bazuco Fritoli, Fabio Henrique da Silva, Fabiano Beraldi Calmasini Pennefather, 1998). Dysregulations of adrenergic pathwayinduced prostate smooth muscle contraction have been associated with BPH genesis and progression in humans and animals (Lee et al, 2017;Calmasini et al, 2016).…”

Section: Aging-associated Prostate Smooth Muscle Hypercontractility I...mentioning

confidence: 99%

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Aging-associated prostate smooth muscle hypercontractility in rats

Lopes¹,

Fritoli²,

Silva

et al. 2022

Braz. J. Pharm. Sci.

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Benign prostatic hyperplasia (BPH) is a multifactorial disease, highly associated with aging and characterized by increased prostate smooth muscle (PSM) contractility. Animal models have been employed to explore the aging-associated PSM hypercontractility; however, studies have focused in old animals, neglecting the initial alterations in early ages. The determination of prostatic dysfunctions onset is crucial to understand the BPH pathophysiology and to propose new BPH treatments. Considering that PSM contractility in 10-month-old rats has already been explored, the aim of the present study was to characterize the PSM contractility in younger rats. Male Wistar control (3.5-month-old), 6-and 8-month-old rats were used. Concentrationresponse curves to phenylephrine and electrical-field stimulation (EFS) were conducted in prostate from all groups. For the first time, we showed that 6-and 8-month-old rats exhibit PSM hypercontractility. The increased prostate contractility to phenylephrine starts around at 6-month-old, worsening during the aging. The 8-month-old rats exhibited hypercontractility to phenylephrine and EFS compared to the control and 6-month-old groups. Reduced phenylephrine potency was observed in 8-month-old rats, indicating an increased age-dependent prostate sensibility to this agonist. Collectively, our findings support the use of 6-and 8-month-old aged rats as new models to explore prostate hypercontractility in BPH.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Aging-associated Prostate Smooth Muscle Hypercontractility I...mentioning

confidence: 99%

See 1 more Smart Citation

Aging-associated prostate smooth muscle hypercontractility in rats

Lopes¹,

Fritoli²,

Silva

et al. 2022

Braz. J. Pharm. Sci.

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“…The β-adrenoceptor activation counteracts the contractile pathways, contributes physiologically to maintain the prostatic tonus in several species and has been proposed as a new pharmacological therapeutic indication for BPH [37,38]. Studies in the literature have shown that impaired βadrenergic signaling plays a role in prostatic dysfunction in animal models of aging and hypertension [39,40]. However, to the best of our knowledge, no previous study evaluated this signaling pathway in prostatic tissue under obesity conditions.…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 9 regulates metabolic profile and contributes to obesity-induced benign prostatic hyperplasia in mice

et al. 2020

Self Cite

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“…Protective effects of resveratrol on male urogenital tract dysfunction LUTS, ED, BPH and prostatitis are the most common UGT diseases. The main risk factors for these diseases include arterial hypertension, obesity, diabetes and ageing, which itself increases inflammation and oxidative status, thereby worsening the incidence and/or progression of UGT diseases (19)(20)(21) . Within this context, resveratrol has emerged as a potential candidate for the treatment of such diseases.…”

Section: Putative Mechanisms Of Action Of Resveratrolmentioning

confidence: 99%

Efficacy of resveratrol in male urogenital tract dysfunctions: an evaluation of pre-clinical data

et al. 2021

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Resveratrol is a polyphenol found naturally in fruits and plants. Recently, studies in humans and animal models have suggested beneficial properties of this polyphenol, such as improvements to metabolic and lipid profiles, along with antioxidant, anti-inflammatory and anti-proliferative effects. In the urogenital tract (UGT), resveratrol has also been tested clinically and experimentally as a therapeutic drug in several diseases; however, the translational efficacy of resveratrol, especially in UGT, is still a matter of debate. In the present review, we address the pre-clinical efficacy of resveratrol in UGT-related dysfunctions, focusing on lower urinary tract symptoms, non-cancerous prostatic disease (benign prostatic hyperplasia and prostatitis) and erectile dysfunction. In vitro studies indicate that resveratrol reduces inflammatory markers and oxidative stress, and improves endothelial function in UGT organs and cells isolated from humans and animals. Despite displaying low oral bioavailability, in vivo administration of resveratrol largely improves erectile dysfunction, benign prostatic hyperplasia, prostatitis and voiding impairments, as evidenced in different animal models. Resveratrol also acts as a microbiota modulator, which may explain some of its beneficial effects in vivo. In contrast to the large amount of pre-clinical data, there are insufficient clinical trials to establish resveratrol treatment efficacy in human UGT-related diseases. In summary, we provide an overview of the in vivo and in vitro efficacy of resveratrol in animal and human UGT dysfunctions, which may support future clinical trials.

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Implication of Rho‐kinase and soluble guanylyl cyclase enzymes in prostate smooth muscle dysfunction in middle‐aged rats

Cited by 8 publications

References 31 publications

Aging-associated prostate smooth muscle hypercontractility in rats

Aging-associated prostate smooth muscle hypercontractility in rats

Toll-like receptor 9 regulates metabolic profile and contributes to obesity-induced benign prostatic hyperplasia in mice

Efficacy of resveratrol in male urogenital tract dysfunctions: an evaluation of pre-clinical data

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