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Protective effect of tadalafil on the functional and structural changes of the rat ventral prostate caused by chronic pelvic ischemia
Author(s) -
Zarifpour Mona,
Nomiya Masanori,
Sawada Norifumi,
Andersson KarlErik
Publication year - 2015
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22909
Subject(s) - tadalafil , medicine , ischemia , prostate , hyperplasia , urology , phenylephrine , endocrinology , erectile dysfunction , cancer , blood pressure
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.