Characterization of silodosin and naftopidil in the treatment of bladder dysfunction in the spontaneously hypertensive rat

Saito, Motoaki; Shimizu, Shogo; Ohmasa, Fumiya; Oikawa, Ryo; Tsounapi, Panagiota; Dimitriadis, Fotios; Kinoshita, Yukako; Satoh, Keisuke

doi:10.1002/nau.22297

Cited by 21 publications

(25 citation statements)

References 24 publications

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“…Saito et al reported that bladder blood flow in the spontaneously hypertensive rat is significantly lower than that in the normotensive Wistar rat, and that vasodilators such as nicorandil (K ATP channel opener and NO donor) increase the bladder blood flow in the spontaneously hypertensive rat (21). Furthermore, treatment with naftopidil increased the bladder blood flow in a dose-dependent manner in the spontaneously hypertensive rat group (22). These results may also support our data which relationships between bladder blood fluid and NOx.…”

Section: Discussionmentioning

confidence: 99%

“…Naftopidil, the alpha 1A/D-adrenoceptor antagonist, has been widely used to BPH because it reduces resistance in the prostatic urethra (31). Multiple studies using rats have shown that naftopidil inhibits the micturition reflex after oral administration (9,22), intravenous injection (2), injection into the medial frontal lobe (14), and after injection into the subarachnoid space at the lumbosacral cord level (26). As naftopidil can inhibit the release of adenosine triphosphate (ATP) from the bladder epithelium (8,27), it may facilitate the afferent nerves and evoke the micturition reflex.…”

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confidence: 99%

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Naftopidil improves locomotor activity and urinary frequency in rats with pelvic venous congestion

Sugaya¹,

Nishijima²,

Kadekawa³

et al. 2016

Biomed. Res.

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The α1D/A receptor antagonist, naftopidil, inhibits micturition reflex by acting on various different sites. We examined the effects of naftopidil on bladder activity and changes in the induced urinary frequency using female rats with pelvic venous congestion (PC). Twenty-four female rats were divided into sham, PC, and PC/naftopidil groups. After anesthetizing rats in the PC and PC/naftopidil groups, the bilateral common iliac veins and uterine veins were ligated. Rats in the sham and PC groups were fed a standard diet, while rats in the PC/naftopidil group were fed diets containing 0.04% naftopidil. After 4 weeks of treatment, locomotor activity, urinary nitric oxide metabolites (NOx), continuous cystometry, and plasma monoamine measurements were performed. PC rats exhibited a decrease of locomotor activity, a shorter interval between bladder contractions on continuous cystometry, and decreased urinary NOx and plasma serotonin levels than the sham rats. The PC/naftopidil rats exhibited an increase of locomotor activity, a longer interval between bladder contractions, and increased urinary NOx and plasma serotonin levels. Therefore, naftopidil might improve bladder dysfunction induced by pelvic venous congestion due to several actions in the central nervous system and bladder tissue, as well as acting as an α1 blocker to cause pelvic venous dilation.Unilateral or bilateral ovarian vein incompetence can cause pelvic congestion syndrome, which induces chronic pain, irritable bladder, dysfunction of the pelvic organs, or vulval varices and varicose veins in the lower limbs (1, 5, 7). Our previous study demonstrated that chronic prostatitis and stress urinary incontinence were related to the existence of vena cava reflux caused by tricuspid regurgitation (28). When we examined a female case with pelvic congestion syndrome using external iliac venography, we found that pelvic venous congestion occurred with tricuspid regurgitation and without pelvic venous valves (25). Our previous studies have also demonstrated that ligation of the bilateral common iliac veins in male rats or ligation of the bilateral common iliac veins and uterine veins in female rats induced changes in the urinary frequency and low locomotor activity (30). As compared to the intact rats, these surgically altered rats exhibited a bladder blood flow decrease that was about 80% of the flow in the intact bladder. Therefore, pelvic venous congestion may be one of the causes of pelvic ischemia, and might be related to several lower urinary tract symptoms/diseases. When examining hypertension, the relevance of lower urinary tract symptoms and their association with hypertension need to be taken into consideration. Spontaneously hypertensive rats have been shown to have a significantly lower bladder capacity and voiding volume (24), and these rats also exhibit

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Naftopidil improves locomotor activity and urinary frequency in rats with pelvic venous congestion

Sugaya¹,

Nishijima²,

Kadekawa³

et al. 2016

Biomed. Res.

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“…(Nic3 and Nic10, respectively). Upon reaching 18 weeks of age, the blood pressure and heart rate were measured by warming the whole animal body without anesthesia by the tail cuff method (BP-98A-L, Softron, Tokyo, Japan) according to our previous reports1540. In short, measurements of blood pressure were performed three times, and the average values were adopted as their individual values.…”

Section: Methodsmentioning

confidence: 99%

Prostatic ischemia induces ventral prostatic hyperplasia in the SHR; possible mechanism of development of BPH

Saito

Tsounapi

Oikawa

et al. 2014

Sci Rep

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In the light of increasing evidence that benign prostatic hyperplasia is associated with cardiovascular disease, we have investigated the relationship between prostatic blood flow and prostatic hyperplasia in the spontaneously-hypertensive-rat (SHR). Twelve-week-old male SHRs were treated with nicorandil for six weeks. Wistar-Kyoto rats were used as controls. Six weeks after nicorandil treatment, blood pressure and the prostatic blood flow were estimated, and tissue levels of malondialdehyde, HIF-1α, TGF-β1, bFGF, dihydrotestosterone, and α-SMA were measured. SHRs showed significant increases in blood pressure, tissue levels of malondialdehyde, HIF-1α, TGF-β1, bFGF, α-SMA and a significant decrease in the prostatic blood flow. Although treatment with nicorandil failed to alter the blood-pressure and α-SMA, it significantly ameliorated the increased levels of malondialdehyde, HIF-1α, TGF-β1, and bFGF. There were no significant differences in tissue levels of dihydrotestosterone among any groups. These data indicate that development of prostatic hyperplasia may be associated with prostatic hypoxia, which nicorandil prevents via its effect to increase the blood flow.

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“…However, although spontaneously hypertensive rats exhibit bladder ischemia, the nerve fiber density of the bladder (base, body, and dome) of spontaneously hypertensive rats is higher than that of normal controls [26] . In this model, α 1A -adrenoceptor-selective antagonists also reduce nerve growth factor level [11] .…”

Section: Discussionmentioning

confidence: 81%

“…α 1 -Adrenoceptor antagonists induce increases in bladder blood flow (BBF) and bladder capacity in LUTS patients [9] . Treatment with α 1A -adrenoceptor-selective drugs but not α 1D -adrenoceptor-selective drugs improves BBF in animal models, such as bladder outlet obstruction [10] , spontaneously hypertensive rats [11,12] , and CBI [13] . The distributions of the various α 1 -adrenoceptor subtypes in each tissue have been reported [14] .…”

Section: Introductionmentioning

confidence: 99%

Silodosin, an α1A-Adrenoceptor Antagonist, May Ameliorate Ischemia-Induced Bladder Denervation and Detrusor Dysfunction by Improving Bladder Blood Flow

Goi

Tomiyama²,

Maruyama³

et al. 2016

Pharmacology

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Background/Aims: This study was performed to investigate the detailed mechanism underlying the effects of the selective α_1A-adrenoceptor antagonist, silodosin, on bladder function in a rat model of atherosclerosis-induced chronic bladder ischemia (CBI). Methods: The CBI model was prepared by balloon endothelial injury of the bilateral iliac arteries in male rats. Using an osmotic pump, the CBI rats received either silodosin or vehicle alone subcutaneously for 8 weeks. Rats received a 2% cholesterol diet throughout the experiment. Bladder blood flow (BBF) was measured. Immunohistochemical staining was performed to determine the nerve distribution and nerve growth factor expression in the bladder. Bladders were used for muscle strip contraction analysis. The expression levels of muscarinic M2 and M3 receptors were measured. Results: Silodosin abrogated the decrease in BBF in CBI rats. Silodosin prevented the decrease in nerve distribution and increase in nerve growth factor expression in the CBI model. Bladder contractile response was reduced in the CBI group. Silodosin ameliorated the effect on the bladder contractile response. The level of muscarinic M3 receptor mRNA present in the bladder of CBI rats was increased by silodosin. Conclusion: The results of this study suggest that silodosin ameliorates the denervation of the bladder and effects on detrusor contractile function under ischemic conditions by restoring BBF.

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Characterization of silodosin and naftopidil in the treatment of bladder dysfunction in the spontaneously hypertensive rat

Abstract: Our data suggest that both silodosin and naftopidil improve hypertension-related bladder dysfunction in the SHR, and naftopidil but not silodosin improves urinary frequency in the light-cycle due to inhibition of urine production.

Cited by 21 publications

References 24 publications

<b>Naftopidil improves locomotor activity and urinary frequency in rats with pelvic venous </b><b>congestion </b>

<b>Naftopidil improves locomotor activity and urinary frequency in rats with pelvic venous </b><b>congestion </b>

Prostatic ischemia induces ventral prostatic hyperplasia in the SHR; possible mechanism of development of BPH

Silodosin, an α<sub>1A</sub>-Adrenoceptor Antagonist, May Ameliorate Ischemia-Induced Bladder Denervation and Detrusor Dysfunction by Improving Bladder Blood Flow

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