ABSTRACT. Mirodenafil (SK3530) is a new potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5). Recent clinical trials have demonstrated that mirodenafil is an effective treatment for erectile dysfunction. Its mechanism of action is enhancement of nitric oxide (NO) induced cGMP formation resulting in significant relaxation of the corpus cavernosum (CC). The aim of this study was to investigate the oral efficacy of mirodenafil in an acute spinal cord-injured rabbit model. Mirodenafil or sildenafil citrate was given orally to male rabbits with a surgical transection of the spinal cord at the L2-L4 lumbar vertebra or ischemic-reperfusion spinal cord injury (SCI). Erections were evaluated in a time-course manner by measuring the length of the uncovered penile mucosa. In the transection SCI model, penile erections were induced at 0.3, 1 and 3 mg/kg of mirodenafil but sildenafil only showed an erectile response at 3 mg/kg. The effects of 1 and 3 mg/kg of mirodenafil were significantly increased by intravenous injection of sodium nitroprusside (SNP), a nitric oxide donor. In the ischemic-reperfusion injury model, 3 mg/kg of either mirodenafil or sildenafil produced a penile erection response. After injection of SNP, the lengths of immediate penile erections were significantly increased in the 1 and 3 mg/kg mirodenafil and 3 mg/kg sildenafil groups. The onset of erectile activity was faster with mirodenafil than with sildenafil citrate. These results demonstrate that mirodenafil may be useful for treating erectile dysfunction in patients with a spinal cord injury. KEY WORDS: mirodenafil, penile erection, phosphodiesterase inhibitor, SK3530, spinal cord injury.J. Vet. Med. Sci. 70(11): 1199-1204, 2008 The advent of phosphodiesterase type 5 (PDE5) inhibitors as oral therapy for erectile dysfunction (ED) ushered in a revolution in clinical management of this condition. Oral ED medications influence the complex neurological, vascular and humoral process underlying penile erection. PDE5 inhibitors influence local regulatory mechanisms of erection, potentiating the smooth muscle relaxing effects of nitric oxide (NO) on resistance arteries and trabecular smooth muscle within the corpus cavernosum [4].Across the world, approximately 152 million men have ED, including about 31 million men in Europe and 18 million men in the US [6,24]. With anticipated increases in the median ages of Western industrialized societies and population growth in developing nations, the number of cases is projected to increase by about 170 million worldwide over the next 25 years. A wide variety of treatment options are now available for patients with ED, ranging from hormone replacement, counseling, non-invasive devices and oral therapies to injectable agents, penile implants and vascular surgery. As a result, almost all men with ED of any type can receive effective treatment. The process of care model designates counseling, vacuum pump, and PDE 5 inhibitors such as sildenafil as first-line options for ED in the primary care s...

Tight junctions (TJs) in inter-Sertoli junctional areas and epididymal epithelia build up the blood-testis barrier (BTB) and the blood-epididymal barrier (BEB), respectively. In this study, the expression of occludin, an integral member of the TJs, was examined in testis and different regions of epididymis of Lepus sinensis coreanus, an Korean wild rabbit species. In testis, intense occludin immunoreactivity was found in the basally located inter-Sertoli junctional area together with diffused immunoreactivity of occludin in the cytoplasm of Sertoli cells. It can be suggested that occludin is one of the robust elements of BTB in seminiferous tubules of rabbit testis. In proximal and distal caput epididymis, occludin immunoreactivity was found in the lateral as well as apical contacts of epithelial cells. In corpus epididymis, intense occludin immunoreactivity was found in the basolateral as well as apical contacts of epithelial cells together with cytoplasmic signal. In cauda epididymis, occludin immunoreactivity in luminal epithelia was relatively strong but largely found in the cytoplasm. This suggests that intriguing regulatory mechanisms differentially recruit occludin to the TJ in the different regions of epididymal epithelia. The differences in the subcellular localization as well as expression levels of occludin among the epididymal segments may reflect differential paracellular permeability of epithelia along the epididymal tubules and be correlated with sperm maturation in rabbit. In Western blot, a major form of occludin was MW 62 kDa together with small fragments of MW 34-39 kDa in testis and epididymis, suggesting the peptide cleavage of occludin. This is the first report on the molecular nature of TJs in a wild rabbit testis and epididymis.

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