Improvement in Bladder Storage Function by Tamsulosin Depends on Suppression of C-Fiber Urethral Afferent Activity in Rats

Yokoyama, Osamu; Yusup, Anwar; Oyama, Nobuyuki; Aoki, Yoshitaka; Miwa, Yoshiji; Akino, Hironobu

doi:10.1016/j.juro.2006.09.076

Cited by 59 publications

(49 citation statements)

References 17 publications

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“…7,13 Regarding EP1 receptor and bladder function, it is suggested that intravesical PGE2 promotes micturition reflex by stimulating C-fiber afferent nerves via EP1 receptor. 14,15 These previous studies and the present study indicate that the action of PGE2 via EP1 receptor has an important role in the development of bladder pain and urinary frequency in ulcer-type IC/BPS.…”

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confidence: 69%

Evaluation of Prostaglandin E2 and E-Series Prostaglandin Receptor in Patients with Interstitial Cystitis

et al. 2015

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Runninghead: Involvement of prostaglandin E2 in interstitial cystitisKey words: bladder pain syndrome, interstitial cystitis, prostaglandin E2 ABSTRACT (250 words)Purpose: To examine the precise role of prostaglandin E2 (PGE2) and E-series prostaglandin (EP) receptor in the pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS). Materials and Methods:Twenty female patients with IC/BPS (11 ulcer-type and 9 non ulcer-type), 9 female controls with other urological diseases who needed cystoscopic procedure, and 10 normal female volunteers were enrolled. O'Leary-Sant Score (OSS) for symptoms and problems and voluntary urine for PGE2 analysis were obtained from all objectives. Under anesthesia, the bladder was distended by saline in a stepwise fashion (from 100 ml to maximum capacity) in patients with IC/BPS, and the infused saline was retrieved each time for PGE2 analysis. We also measured PGE2 and expression of EP receptors mRNA in bladder biopsy tissue in patients with IC/BPS.Results: Symptoms and problems index in patients with ulcer-type was significantly higher than those with non ulcer-type. Urinary PGE2 in patients with ulcer-type was significantly higher than those with non ulcer-type and normal volunteers. PGE2 level in retrieved saline in patients with ulcer-type increased depending on infusion volume, but not in those with non ulcer-type. PGE2 content in bladder biopsy tissue was significantly higher in patients with ulcer-type than controls. In patients with ulcer-type, expression of EP1 and EP2 mRNA was significantly higher than controls. Conclusions:Overproduction of PGE2 in the bladder seems to play a pathophysiological role in patients with ulcer-type IC/BPS via EP1 and EP2 receptors. Localized blockade of the action of PGE2 may lead to relieving symptoms in patients with ulcer-type IC/BPS. TEXTInterstitial cystitis/bladder pain syndrome (IC/BPS), non-specific inflammatory disease of the bladder, presents with a constellation of symptoms including urinary frequency, urgency and bladder pain. IC/BPS has 2 distinct subtypes based on cystoscopic evaluation. One is ulcer-type and another is non ulcer-type. In patients with IC/BPS and controls, samples were taken by cystoscopic procedure under general or spinal anesthesia. In patients with IC/BPS, the bladder was distended in a stepwise fashion with a drip infusion of saline. Saline bottles were placed at 80cm height from the symphysis pubis. First, cystoscope was inserted and the bladder was emptied. Then 100ml of saline was infused into the bladder as first step and maintained for 5 minutes. All of the infused saline was retrieved and sampled. Next, 200ml of saline was infused, maintained for 5 minutes, retrieved and sampled as second step. Third step and final step were similarly performed after 300ml saline infusion and maximum bladder capacity. Maximum bladder capacity was defined as bladder capacity at the time when saline infusion stopped after reaching 80cmH2O. In control patients, infused saline only at first step (100ml infusi...

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confidence: 69%

Evaluation of Prostaglandin E2 and E-Series Prostaglandin Receptor in Patients with Interstitial Cystitis

et al. 2015

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“…Recently, it was reported that α1AR antogonists are effective in the treatment of storage symptoms [16]. This suggests that not only the α1D AR but also the α1A AR may have an important role in the development of storage symptoms.…”

Section: Discussionmentioning

confidence: 99%

Effects of Spinal and Peripheral Injection of α1A or α1D Adrenoceptor Antagonists on Bladder Activity in Rat Models with or without Bladder Outlet Obstruction

et al. 2011

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PurposeAntagonists of α1-adrenergic receptors (α1ARs) relax prostate smooth muscle and relieve voiding and storage symptoms. Recently, increased expression of α1ARs with change of its subtype expression has been proved in bladder outlet obstruction (BOO). To search for the evidence of changes in α1ARs subtype expression and activity in the peripheral and spinal routes, the effects of spinal and peripheral administration of tamsulosin (an α1A/D-selective AR), naftopidil (an α1A/D-selective AR), and doxazosin (non-selective AR) on bladder activity were investigated in a rat model with or without BOO.MethodsA total of 65 female Sprague-Dawley rats were divided into the BOO surgery group (n=47) and the sham surgery group (n=18). After 6 weeks, cystometry was assessed before and after intrathecal and intra-arterial administrations of tamsulosin, naftopidil, and doxazosin.ResultsAfter intra-arterial administrations of all three drugs, bladder capacity (BC) was increased and maximal intravesical pressure (Pmax) was decreased in both BOO and the sham rat models (P<0.05). After intrathecal administration of all three drugs, BC was increased and Pmax was decreased in only the BOO group. The episodes of involuntary contraction in the BOO rat models were decreased by intra-arterial administration (P=0.031). The increase of BC after intrathercal and intra-arterial administrations of α1ARs was significantly greater in the BOO group than in the sham group (P=0.023, P=0.041). In the BOO group, the increase of BC and decrease in Pmax were greater by intra-arterial administration than by intrathecal administration (P=0.035). There were no significant differences of the degrees of changes in the cystometric parameters among the three different α1ARs.ConclusionsUp-regulations of the α1ARs in BOO were observed by the greater increases of BC after α1AR antagonist administrations in the BOO group than in the sham group. However, there were no subtype differences of the α1ARs in functional parameters of bladder activity. In addition, α1ARs also act on the lumbosacral cord which implies that the sensitivity of α1ARs is increased in pathologic models such as BOO. Further evaluation including differential expression of α1ARs in BOO models are need.

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“…Likewise, in a rat model of detrusor overactivity caused by topical intraurethral application of prostaglandin E 2 , the action of tamsulosin depended on the suppression of C-fiber urethral afferent activity [2] . These studies showed that ␣ 1 -AR antagonists inhibit some part of bladder afferent nerves under pathological situations.…”

Section: Effects Of ␣ -Blockers On Afferent Pathwaysmentioning

confidence: 99%

Effect of Long-Term Prazosin and Yohimbine Administration on c-Fos Expression in Spinal Neurons: Inhibitory Effect of Alpha-1 and Alpha-2 Adrenoceptors on Afferents from the Lower Urinary Tract

Haga

Shishido²,

Yanagida³

et al. 2011

Urol Int

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Introduction: To investigate the effects of long-term administration of the α₁-adrenoceptor antagonist prazosin and the α₂-adrenoceptor antagonist yohimbine on afferent inputs from the lower urinary tract by evaluating c-Fos expression in the spinal cord. Materials and Methods: Prazosin or yohimbine was administered for 4 weeks in rats using an osmotic pump. Effects of these agents on urodynamic parameters were determined by continuous cystometry in conscious rats. After cystometry, c-Fos expression in the dorsal horn of the L6 spinal cord was measured by immunohistochemistry. Results: The administration of prazosin (0.12 mg/kg/day) or yohimbine (0.10 mg/kg/day) significantly increased micturition interval and bladder capacity, but did not affect micturition pressure and residual urine volume. The numbers of c-Fos-positive neurons in the dorsal horn were significantly lower in rats that received prazosin than in controls. Yohimbine reduced the number of c-Fos-positive neurons in part of the dorsal horn. Conclusions: Long-term administration of prazosin and yohimbine at clinically recommended doses can exert inhibitory effects on afferent pathways from the lower urinary tract during the storage phase. These reductions of the afferent input result in the increased bladder capacity and increased micturition interval.

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Improvement in Bladder Storage Function by Tamsulosin Depends on Suppression of C-Fiber Urethral Afferent Activity in Rats

Abstract: These results suggest that prostaglandin E(2) enhances the micturition reflex through C-fiber afferents and tamsulosin had an inhibitory effect on the C-fiber urethral afferent nerves, thereby improving bladder storage function.

Cited by 59 publications

References 17 publications

Evaluation of Prostaglandin E2 and E-Series Prostaglandin Receptor in Patients with Interstitial Cystitis

Evaluation of Prostaglandin E2 and E-Series Prostaglandin Receptor in Patients with Interstitial Cystitis

Effects of Spinal and Peripheral Injection of α1A or α1D Adrenoceptor Antagonists on Bladder Activity in Rat Models with or without Bladder Outlet Obstruction

Effect of Long-Term Prazosin and Yohimbine Administration on c-Fos Expression in Spinal Neurons: Inhibitory Effect of Alpha-1 and Alpha-2 Adrenoceptors on Afferents from the Lower Urinary Tract

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