A Selective α1A-Adrenoceptor Antagonist Inhibits Detrusor Overactivity in a Rat Model of Benign Prostatic Hyperplasia

Tatemichi, Satoshi; Akiyama, Katsuyoshi; Kobayashi, Mamoru; Yamazaki, Yoshinobu; Yokoyama, Osamu; Uruno, Tsutomu

doi:10.1016/j.juro.2006.04.029

Cited by 40 publications

(33 citation statements)

References 18 publications

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“…The physiological outcome of these changes with respect to mouse voiding function was not previously examined. Bladder outlet obstruction increases voiding pressure in men and rodents (2,28,31,33). In the current study, a folic acid-enriched diet failed to moderate the TϩE2-induced increase in prostate wet weight and threshold pressure (Figs.…”

Section: Discussionmentioning

confidence: 99%

Impact of a folic acid-enriched diet on urinary tract function in mice treated with testosterone and estradiol

Keil

Abler

Altmann

et al. 2015

American Journal of Physiology-Renal Physiology

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CM. Impact of a folic acid-enriched diet on urinary tract function in mice treated with testosterone and estradiol. Am J Physiol Renal Physiol 308: F1431-F1443, 2015. First published April 8, 2015 doi:10.1152/ajprenal.00674.2014.-Aging men are susceptible to developing lower urinary tract symptoms, but the underlying etiology is unknown and the influence of dietary and environmental factors on them is unclear. We tested whether a folic acid-enriched diet changed urinary tract physiology and biology in control male mice and male mice with urinary dysfunction induced by exogenous testosterone and estradiol (TϩE2), which mimics changing hormone levels in aging humans. TϩE2 treatment increased mouse urine output, time between voiding events, and bladder capacity and compliance. Consumption of a folic acid-enriched diet moderated these changes without decreasing prostate wet weight or threshold voiding pressure. One potential mechanism for these changes involves water balance. TϩE2 treatment increases plasma concentrations of anti-diuretic hormone, which is offset at least in part by a folic acid-enriched diet. Another potential mechanism involves neural control of micturition. The folic acid-enriched diet, fed to TϩE2-treated mice, increased voiding frequency in response to intravesicular capsaicin infusion and increased mRNA abundance of the capsaicinsensitive cation channel transient receptor potential vanilloid subfamily member 1 (Trpv1) in L6 and S1 dorsal root ganglia (DRG) neurons. TϩE2 treatment and a folic acid-enriched diet also modified DNA methylation, which is capable of altering gene expression. We found the enriched diet increased global DNA methylation in dorsal and ventral prostate and L6 and S1 DRG. Our results are consistent with folic acid acting to slow or reverse TϩE2-mediated alteration in urinary function in part by normalizing water balance and enhancing or preserving afferent neuronal function. cystometry; mouse model; voiding; folic acid; epigenetics BENIGN PROSTATIC HYPERPLASIA (BPH) is characterized by benign enlargement of the prostate. BPH is often associated with lower urinary tract symptoms (LUTS) that can include increased urinary frequency and urgency, increased nighttime urination, pain, weak stream, hesitancy, dribbling, incomplete emptying, and incontinence (25). Approximately 70% of men over age 70 experience BPH and/or LUTS (5).Aging-related changes in plasma hormone concentrations are potential driving factors in the onset and progression of BPH and LUTS. Plasma testosterone concentration declines as men age, while estradiol concentration remains the same or even rises (13). Rodents treated with testosterone and estradiol (TϩE2) to mimic this aging-associated hormonal milieu develop enlarged prostates, narrow prostatic urethras, and retain urine in a manner consistent with bladder outlet obstruction (4, 27).Our group and others have been elucidating proliferative growth pathways in developing prostates with the goal of examining whether these pathways are activated inappropri...

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Section: Discussionmentioning

confidence: 99%

Impact of a folic acid-enriched diet on urinary tract function in mice treated with testosterone and estradiol

Keil

Abler

Altmann

et al. 2015

American Journal of Physiology-Renal Physiology

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“…Cystometric studies were performed according to a procedure similar to that described previously [23,24]. Rats (30-42 weeks old) were anesthetized with 25% urethane (1.0 g/kg intraperitoneally).…”

Section: Methodsmentioning

confidence: 99%

“…After stabilization of the voiding pattern, the micturition cycles were recorded before and after the intravenous administration of test compounds. The doses of test drugs were determined with reference to previous reports [23,25]. …”

Section: Methodsmentioning

confidence: 99%

Effects of Silodosin, an α<sub>1A</sub>-Adrenoceptor Antagonist, and Distigmine, an Acetylcholinesterase Inhibitor, and Their Combined Effects on Impaired Voiding Function in Zucker Diabetic Fatty Rats

et al. 2015

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Background/Aims: To evaluate the effects of silodosin (α_1A-adrenoceptor antagonist) and distigmine (acetylcholinesterase inhibitor), alone or in combination, on voiding dysfunction in Zucker diabetic fatty (ZDF) rats, a type 2 diabetes model, by pressure flow study. Methods: Male ZDF rats were anesthetized with urethane and a catheter was implanted into the bladder through the dome. Saline was continuously infused into the bladder at 6 ml/h to induce the micturition reflex. Intravesical pressure and micturition volume were recorded continuously and various urodynamic parameters were calculated using a waveform analysis system. Results: Increased bladder capacity, residual volume, and urethral resistance and decreased maximum detrusor contraction velocity and urine flow rate, considered to be detrusor underactivity-like symptoms, were observed in ZDF rats. Although both silodosin and distigmine improved impaired voiding function, administration of both drugs in combination was more effective than either drug alone. Conclusions: ZDF rats showed symptoms suggestive of detrusor underactivity, and silodosin tended to ameliorate these symptoms in ZDF rats. These results suggested that an α_1A-adrenoceptor antagonists may be effective against the voiding disorder accompanying not only bladder outlet obstruction but also deficiency of bladder function. Moreover, combined administration of an α_1A-adrenoceptor antagonist with an acetylcholinesterase inhibitor may have additive efficacy in clinical use.

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“…Improvement in detrusor overactivity may reflect secondary effects due to a relief of prostatic urethral tension. 40 Another possible mechanism for the improvement of detrusor overactivity is that obstruction causes ischemia (and reperfusion) that leads to detrusor overactivity and bladder dysfunction. [58][59][60] The α 1A -AR may predominate in the small arteries, including the bladder arteries of elderly patients and α 1A -AR antagonist may therefore increase blood flow to the bladder and thus alleviate detrusor overactivity.…”

Section: Dovepressmentioning

confidence: 99%

Management of benign prostatic hyperplasia with silodosin

Yamanishi¹

2009

OAJU

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A Selective α1A-Adrenoceptor Antagonist Inhibits Detrusor Overactivity in a Rat Model of Benign Prostatic Hyperplasia

Cited by 40 publications

References 18 publications

Impact of a folic acid-enriched diet on urinary tract function in mice treated with testosterone and estradiol

Impact of a folic acid-enriched diet on urinary tract function in mice treated with testosterone and estradiol

Effects of Silodosin, an α<sub>1A</sub>-Adrenoceptor Antagonist, and Distigmine, an Acetylcholinesterase Inhibitor, and Their Combined Effects on Impaired Voiding Function in Zucker Diabetic Fatty Rats

Management of benign prostatic hyperplasia with silodosin

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