Histopathological effects of sildenafil citrate on rat corpus cavernosum
Introduction
Sildenafil citrate has been shown to be highly effective in the treatment of erectile dysfunction and it is used to treat impotence of various etiologies with good tolerance.
The penis is composed of three columns of erectile tissue each enclosed by its own dense fibrous connective tissue (Fig. 1). Corpora cavernosa, two of the three columns of erectile tissue, are positioned dorsally, and the third column, the corpus spongiosum, is positioned ventrally. The corpus spongiosum surrounds the urethra. The three corpora are surrounded by loose connective tissue and smooth muscle cells. The vascular spaces of the corpora cavernosa are larger centrally and smaller peripherally. All corpora include vascular spaces that receive blood from branches of the deep dorsal and cavernosal arteries of the penis (Fig. 1).
Sildenafil citrate, a pyrazolo-pyrimidinyl-methylpiperazine compound, is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5; Jeremy et al., 1997; Ballard et al., 1998). It enhances the relaxant effect of nitric oxide (NO) on the corpus cavernosum by inhibiting PDE5, which is responsible for degradation of cGMP in the tissue (Medina et al., 2000). Inhibition of PDE5 by sildenafil citrate increases cGMP levels in the corpora, causing smooth muscle relaxation and blood flow into the penis during the local release of NO due to sexual stimulation. This is the main action of sildenafil citrate on the physiologic mechanisms of erection (Medina et al., 2000; Moreira et al., 2000; Pfizer, 2000). However, we do not know the long-term effects of the use of sildenafil citrate on the corpora of the penis. In addition, histopathological and ultrastructural effects of the use of sildenafil citrate on corpus cavernosum components are not known. Therefore, we decided to investigate the histopathological and ultrastructural effects of sildenafil citrate in the rat corpus cavernosum using light and electron microscopical techniques.
Section snippets
Animals
Twenty male 10–12-week-old Wistar rats with an average weight of 250 g were used. Rats were fed standard diet and were divided into two groups of 10 rats each. The first group was used as control and the second group was treated with 2 mg/kg body weight/day sildenafil citrate orally via gavage on alternate days (3 days in a week) for 4 weeks (Ishikura et al., 2000). All male rats were coupled with female rats overnight for sexual activity only on the days when sildenafil was given. The impact of
Results
The histological analysis revealed that the corpus cavernosum, which is the main anatomic structure used during erection and consists of numerous vascular spaces with wide and irregular shaped lumina that are lined by endothelial cells, was elongated and the number of vascular spaces was increased in sildenafil-treated rats (Fig. 2). The amount of connective tissue in the corpus cavernosum was clearly increased and dense collagen and smooth muscle fibers were observed in treated rats. The
Discussion
Sildenafil citrate is used for the treatment of erectile dysfunction with good tolerance and few side effects. Previously published studies demonstrated that the most common adverse effects of sildenafil citrate were associated with systemic effects such as vasodilatation causing headache, flushing, dyspepsia and nasal congestion (Goldstein et al., 1998; Kirby et al., 1999; Hackett and Gingell, 1999). So far, effects of sildenafil citrate have not been associated with local adverse effects such
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Effect of chronic administration of sildenafil citrate (Viagra) on the histology of the retina and optic nerve of adult male rat
2017, Tissue and CellCitation Excerpt :The increased risk of retinal toxicity after repeated exposure to sildenafil might be attributed to the chronically elevated levels of cyclic guanosine monophosphate (cGMP) which inhibits the breakdown of nitric oxide (Behn and Potter, 2001). Also, the thickened basal lamina of the blood capillaries observed in the retina and optic nerve of sildenafil treated group in this study has been previously reported by Gümüş et al. (2004) in sildenafil citrate treated rat corpus cavernosum. Moreover, this study revealed increased CD31 (endothelial marker) expression in the INL, IPL and GCL of the retina, and in the optic nerve of sildenafil citrate treated group.
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