Protective effect of tadalafil on the functional and structural changes of the rat ventral prostate caused by chronic pelvic ischemia

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

The etiology of Benign Prostatic Hyperplasia (BPH), a common among aged men, is not fully understood, however, in addition to androgens and aging, chronic ischemia has been proposed to contribute. Using an established rat model, we investigated whether chronic ischemia alters the structural and functional properties of the ventral rat prostate, and whether phosphodiesterase type 5 (PDE5) inhibitor (tadalafil) may have a protective action.

Methods

Adult male Sprague-Dawley rats were divided into control, arterial endothelial injury (AI), and AI with tadalafil treatment (AI-tadalafil) groups. AI and AI-tadalafil groups underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet following AI. AI-tadalafil rats were treated with tadalafil (2 mg/kg/day) orally for 8 weeks after AI. The control group received a regular diet. After 8 weeks, animals were sacrificed, and pharmacological and morphological studies on prostate tissues were performed.

Results

Iliac arteries from AI rats displayed neo-intimal formation and luminal occlusion, an effect that was not prevented by tadalafil treatment. In the AI group, there was an obvious epithelial atrophy and a statistically significant increase in collagen fibers compared with the controls. Immunohistochemically, there was an up-regulation of smooth muscle α-actin (SMA). Contractile responses of prostate strips to KCl, electrical field stimulation (EFS), and phenylephrine (PE) were significantly higher after AI than in controls. Chronic treatment with tadalafil prevented the increase in contractile responses in ischemic tissue, and decreased the collagen deposition compared with the AI group.

Conclusions

In this rat model, chronic pelvic ischemia caused distinct functional and morphological changes in the prostate. Prostatic tissue from ischemic animals showed an increased contractile response to electrical and pharmacological stimulation, an increase in SMA, and an increased deposition of collagen. All these changes could be prevented by treatment with the PDE5 inhibitor, tadalafil, suggesting an involvement of cyclic guanosine monophosphate (cGMP). Prostate 75:233–241, 2015. © 2014 The Authors. The Prostate Published by Wiley Periodicals, Inc.

Related collections

Most cited references 34

Record: found
Abstract: found
Article: not found

The correlation between metabolic syndrome and prostatic diseases.

Cosimo De Nunzio, William Aronson, Stephen J. Freedland … (2012)

Metabolic syndrome (MetS), a cluster of several metabolic abnormalities with a high socioeconomic cost, is considered a worldwide epidemic. Recent epidemiologic and clinical data suggest that MetS is involved in the pathogenesis and progression of prostatic diseases such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa). This review evaluates the available evidence of the role of MetS in BPH and PCa development and progression and discusses possible clinical implications for the management, prevention, and treatment of these diseases. A National Center for Biotechnology Information (NCBI) PubMed search for relevant articles published between 1995 and September 2011 was performed by combining the following Patient population, Intervention, Comparison, Outcome (PICO) terms: male, metabolic syndrome, prostate, benign prostatic hyperplasia, prostate cancer, prevention, diagnosis, treatment, and prognosis. Additional references were obtained from the reference list of full-text manuscripts. MetS is a complex, highly prevalent disorder and a worldwide epidemic. Central obesity, insulin resistance, dyslipidemia, and hypertension are the main components of MetS. Notwithstanding all the attempts made to correctly define MetS, a major problem related to most definitions remains the applicability to different populations and ethnic groups. Although there is growing evidence of the association of MetS with the initiation and clinical progression of BPH and PCa, molecular mechanisms and effects on treatment efficacy remain unclear. Further research is required to better understand the role of MetS in BPH and PCa. Data from the peer-reviewed literature suggest an association of MetS with BPH and PCa, although the evidence for a causal relationship remains missing. MetS should be considered a new domain in basic and clinical research in patients with prostatic disorders. Copyright © 2011 European Association of Urology. All rights reserved.

0 comments Cited 114 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Androgens and estrogens in benign prostatic hyperplasia: past, present and future.

Tristan M Nicholson, William Ricke (2016)

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common clinical problems in urology. While the precise molecular etiology remains unclear, sex steroids have been implicated in the development and maintenance of BPH. Sufficient data exists linking androgens and androgen receptor pathways to BPH and use of androgen reducing compounds, such as 5α-reductase inhibitors which block the conversion of testosterone into dihydrotestosterone, are a component of the standard of care for men with LUTS attributed to an enlarged prostate. However, BPH is a multifactorial disease and not all men respond well to currently available treatments, suggesting factors other than androgens are involved. Testosterone, the primary circulating androgen in men, can also be metabolized via CYP19/aromatase into the potent estrogen, estradiol-17β. The prostate is an estrogen target tissue and estrogens directly and indirectly affect growth and differentiation of prostate. The precise role of endogenous and exogenous estrogens in directly affecting prostate growth and differentiation in the context of BPH is an understudied area. Estrogens and selective estrogen receptor modulators (SERMs) have been shown to promote or inhibit prostate proliferation signifying potential roles in BPH. Recent research has demonstrated that estrogen receptor signaling pathways may be important in the development and maintenance of BPH and LUTS; however, new models are needed to genetically dissect estrogen regulated molecular mechanisms involved in BPH. More work is needed to identify estrogens and associated signaling pathways in BPH in order to target BPH with dietary and therapeutic SERMs. Published by Elsevier B.V.

0 comments Cited 79 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Endothelial dysfunction and hypertension in aging.

Yukihito Higashi, Kensuke Noma, Yasuki Kihara (2012)

Hypertension is one of the common diseases in the elderly. The prevalence of hypertension markedly increases with advancing age. Both aging and hypertension have a critical role in cardiovascular and cerebrovascular complications. Although aging and hypertension, either independently or collectively, impair endothelial function, aging and hypertension may have similar cascades for the pathogenesis and development of endothelial dysfunction. Nitric oxide (NO) has an important role in regulation of vascular tone. Decrease in NO bioavailability by endothelial dysfunction would lead to elevation of blood pressure. An imbalance of reduced production of NO or increased production of reactive oxygen species, mainly superoxide, may promote endothelial dysfunction. One possible mechanism by which the prevalence of hypertension is increased in relation to aging may be advancing endothelial dysfunction associated with aging through an increase in oxidative stress. In addition, endothelial cell senescence is also involved in aging-related endothelial dysfunction. In this review, we focus on recent findings and interactions between endothelial function, oxidative stress and hypertension in aging.

0 comments Cited 74 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Prostate

Journal ID (iso-abbrev): Prostate

Journal ID (publisher-id): pros

Title: The Prostate

Publisher: BlackWell Publishing Ltd (Oxford, UK )

ISSN (Print): 0270-4137

ISSN (Electronic): 1097-0045

Publication date (Print): February 2015

Publication date (Electronic): 18 October 2014

Volume: 75

Issue: 3

Pages: 233-241

Affiliations

[1 ]Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine Winston-Salem, North Carolina

[2 ]Department of Urology, Fukushima Medical University School of Medicine Fukushima City, Japan

[3 ]Aarhus Institute of Advanced Studies (AIAS), Aarhus University Aarhus, Denmark

Author notes

Correspondence to:, Karl-Erik Andersson, MD, PhD, AIAS, Aarhus Institute of Advanced Studies, Aarhus University, Høegh-Guldbergs Gade 6B, building 1632, 8000 Aarhus C, Denmark. E-mail: kea@ 123456aias.au.dk

Article

DOI: 10.1002/pros.22909

PMC ID: 4305204

PubMed ID: 25327615

SO-VID: 174dea94-3564-4bef-a395-7e5d22270b93

License:

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Protective effect of tadalafil on the functional and structural changes of the rat ventral prostate caused by chronic pelvic ischemia

Read this article at

Abstract

Background

Methods

Results

Conclusions

Related collections

Karger: Endocrinology

Most cited references 34

The correlation between metabolic syndrome and prostatic diseases.

Androgens and estrogens in benign prostatic hyperplasia: past, present and future.

Endothelial dysfunction and hypertension in aging.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 334

Cited by 10

Most referenced authors 366