Voiding effects mediated by α<sub>2</sub>‐adrenoceptors in the anaesthetized male rat

Streng, Tomi; Santti, Risto; Andersson, Karl‐Erik

doi:10.1111/j.1464-410x.2010.09228.x

Cited by 10 publications

(6 citation statements)

References 17 publications

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“…The ␣ 2 -ARs contribute to the mediation and maintenance of tone in urethral smooth muscles, and thus to resistance to urinary flow [35] . Streng et al [12] presented evidence that in anesthetized rats, intravenous administration of an ␣ 2 -AR antagonist (atipamazole) significantly increased the rhabdosphincter electromyography amplitude and micturition pressure due to facilitated urinary flow resistance. The voiding interval then increased significantly.…”

Section: Discussionmentioning

confidence: 99%

“…However, naftopidil is an ␣ 1 -AR antagonist with weak antagonistic activity for ␣ 2 -AR [11] , leading to the hypothesis that ␣ 2 -AR antagonists may influence afferent pathways of the LUT and improve storage symptom. Although ␣ 2 -ARs are well researched in terms of the efferent pathways to the LUT [12][13][14][15][16] , the function of these receptors in the afferent system does not appear to have been studied.…”

Section: Effects Of ␣ -Blockers On Afferent Pathwaysmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…An ultrasonic flow probe (Probe #ME2PXN; Transonic Systems, Ithaca, NY), connected to a flow meter (TS410; Transonic Systems) was used to measure the UFR. The flow probe was placed around the most distal part of the urethra (31,39).…”

Section: Methodsmentioning

confidence: 99%

Influence of serotonergic mechanisms on the urine flow rate in male rats

Fan

Chen

Hsieh

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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This study extensively examined the role of a 5-HT 1A receptor in controlling voiding function in anesthetized male rats. A simultaneous recording of the intravesical pressure (IVP), external urethral sphincter (EUS)-electromyography (EMG), and urine flow rate (UFR) during continuous cystometry was used. 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), a 5-HT 1A receptor agonist, significantly improved the voiding efficiency, as detected by increases in the evoked contraction amplitude, EUS burst period, and silent period, and decreases in the volume threshold, pressure threshold, and residual volume. Interestingly, the UFR during voiding was reduced by 8-OH-DPAT, as evidenced by decreases in the maximal UFR and mean UFRs of the voiding period, spike duration, and interspike interval. Conversely, treating rats with WAY-100635, a 5-HT1A antagonist, produced effects opposite to those produced by 8-OH-DPAT. These findings suggest that 8-OH-DPAT improved the voiding efficiency by enhancing the detrusor contractile ability and prolonging EUS burst period, which would compensate for the lower UFR, resulting from urethral smooth muscle contractions and longer EUS silent periods during voiding. The present study contributes to our understanding of the role of 5-HT1A receptors in controlling the urine flow rate in male rats. intravesical pressure; external urethral sphincter-electromyography; 8-hydroxy-2-(di-n-propylamino)-tetralin; WAY-100635; voiding efficiency SEROTONIN (5-HYDROXYTRYPTAMINE, 5-HT) comprises 14 structurally different 5-HT receptors in mammalian species, including seven subfamilies (5-HT 1 to 5-HT 7 ) (28). A number of 5-HT receptor subfamilies, particularly 5-HT 1A receptors, located at nerve terminals are involved in the function of the lower urinary tract (LUT) (38). Indeed, these 5-HT receptors-related nerve terminals are distributed in areas of the spinal cord containing afferent and efferent components of LUT neural control centers (8,15,19,24,38). Thus, 5-HT receptors appear to modulate all of the pathways involved in the control of reflex bladder and urethral sphincter activity, including the parasympathetic, sympathetic, and somatic pathways (13).The 5-HT 1A receptor is one of the most extensively investigated agents in functions of the LUT in various animal pharmacological experiments, including rats, guinea pigs, and cats (28). However, contradictory results have generated various interpretations of the functions of this receptor subtype in different animal species. Because the rat model has now gained greater popularity as the main species for investigating functions of the LUT, the effects of a 5-HT 1A receptor agonist on regulating urine storage and micturition reflexes have been extensively investigated in female rats (14, 20 -22, 35). However, few studies have explored these pharmacological effects in male animals. Moreover, our recent studies demonstrated that 8-OH-DPAT, a 5-HT 1A receptor agonist, elevated the urethral pressure (resistance) during the voiding reflex in male rats (1...

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“…Given that the incidence of urethral obstructions in this study is not dose dependent with dexmedetomidine, this would lead us to believe that the alpha 1 receptor cannot be the only receptor involved. Given this, the cause of the obstruction is likely multifactorial with the alpha 2 adrenergic effects of dexmedetomidine resulting in a decreased ability to void the urinary bladder and the alpha 1 adrenergic effects causing urethral sphincter tightening [ 15 ]. At this time, the role of seminal coagulum plugs in this obstructive process is unclear.…”

Section: Discussionmentioning

confidence: 99%

Injectable Anesthesia for Mice: Combined Effects of Dexmedetomidine, Tiletamine-Zolazepam, and Butorphanol

Cagle

Franzi

Epstein

et al. 2017

Anesthesiology Research and Practice

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Anesthetic protocols for murine models are varied within the literature and medetomidine has been implicated in the development of urethral plugs in male mice. Our objective was to evaluate the combination of butorphanol, dexmedetomidine, and tiletamine-zolazepam. A secondary objective was to identify which class of agent was associated with urethral obstructions in male mice. BALB/c male (n = 13) and female (n = 23) mice were assigned to dexmedetomidine and tiletamine-zolazepam with or without butorphanol or to single agent dexmedetomidine or tiletamine-zolazepam. Anesthesia was achieved in 58% (14/24) of mice without butorphanol and in 100% (24/24) of mice with butorphanol. The combination of dexmedetomidine (0.2 mg/kg), tiletamine-zolazepam (40 mg/kg), and butorphanol (3 mg/kg) resulted in an induction and anesthetic duration of 12 and 143 minutes, respectively. Urethral obstructions occurred in 66% (25/38) of trials in male mice that received dexmedetomidine with a mortality rate of 38% (5/13). Tiletamine-zolazepam, when used alone, resulted in a 0% (0/21) incidence of urethral obstructions. Combination use of dexmedetomidine, tiletamine-zolazepam, and butorphanol results in a longer and more reliable duration of anesthesia than the use of dexmedetomidine and tiletamine-zolazepam alone. Dexmedetomidine is not recommended for use in nonterminal procedures in male mice due to the high incidence of urethral obstructions and resultant high mortality rate.

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Voiding effects mediated by α₂‐adrenoceptors in the anaesthetized male rat

Cited by 10 publications

References 17 publications

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

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

Influence of serotonergic mechanisms on the urine flow rate in male rats

Injectable Anesthesia for Mice: Combined Effects of Dexmedetomidine, Tiletamine-Zolazepam, and Butorphanol

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Voiding effects mediated by α2‐adrenoceptors in the anaesthetized male rat

Cited by 10 publications

References 17 publications

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

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

Influence of serotonergic mechanisms on the urine flow rate in male rats

Injectable Anesthesia for Mice: Combined Effects of Dexmedetomidine, Tiletamine-Zolazepam, and Butorphanol

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Voiding effects mediated by α₂‐adrenoceptors in the anaesthetized male rat