To investigate the protective effect of mirabegron on bladder dysfunction in an acute urinary retention rat model.
Materials and methods
Thirty-six 16-week Sprague–Dawley rats were assigned to the mirabegron and normal saline (N/S) groups. Each group of eighteen was divided into sub-groups of 6 for 30 min, 2 h, and 24 h. They were administered mirabegron (10 mg/kg) and N/S daily for 4 weeks, respectively. Mirabegron and N/S groups were divided into sub-groups of 6 rats for 30 min, 2 h, and 24 h. The changes in bladder blood flow were measured using laser Doppler (moorVMS-LDF2). Histopathological examination of the bladder and nitric oxide (NO) measurement were performed.
During the urinary retention phase in the mirabegron group, it showed higher and rapider recovery of blood flow; the lowest at 19.5% ± 3.68% at 3 min, a significant recovery from the lowest value as 23.7 ± 3.4% at 10 min, than that in the N/S group; 15.1 ± 1.84% at 5 min, 23.7 ± 3.4% at 20 min, respectively (P < 0.05). At 30 min, 120 min, and 24 h after reperfusion, the recovery of blood flow in the mirabegron group was significantly higher than that in the N/S group (mirabegron: 41.1 ± 1.7%, 59.9 ± 7.2%, and 89.7 ± 4.4%, N/S: 31.3 ± 2.1%, 47.3 ± 4.5%, 83.9 ± 3.6%, respectively (P < 0.05)). NO levels tended to be higher in the mirabegron group; however, the difference was not statistically significant. Histological examination revealed that the mirabegron group showed recovery close to normal tissue after 24 h.
In an acute urinary retention rat model, mirabegron maintained and restored higher bladder blood flow, resulting in protective and recovery effect after acute urinary retention.
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Acute urinary retention
Benign prostate hyperplasia
Bladder outlet obstruction
Post-void residual urine volume
Abrams P, Cardozo L, Fall M et al (2003) The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology 61:37
Meigs JB, Barry MJ, Giovannucci E et al (1999) Incidence rates and risk factors for acute urinary retention: the health professionals followup study. J Urol 162:376
Gabella G, Uvelius B (1999) Structural changes in the rat bladder after acute outlet obstruction. Scand J Urol Nephrol Suppl 201:32
Saito M, Miyagawa I (2001) Bladder dysfunction after acute urinary retention in rats. J Urol 165:1745
Yildirim A, Onol FF, Haklar G et al (2008) The role of free radicals and nitric oxide in the ischemia-reperfusion injury mediated by acute bladder outlet obstruction. Int Urol Nephrol 40:71
Sawada N, Nomiya M, Hood B et al (2013) Protective effect of a β3-adrenoceptor agonist on bladder function in a rat model of chronic bladder ischemia. Eur Urol 64:664
Mizuno H, Yamamoto T, Okutsu H et al (2010) Effect of tamsulosin on bladder microcirculation in a rat ischemia-reperfusion model, evaluated by pencil lens charge-coupled device microscopy system. Urology 76:1266.e1
Greenland JE, Brading AF (2001) The effect of bladder outflow obstruction on detrusor blood flow changes during the voiding cycle in conscious pigs. J Urol 165:245
Greenland JE, Hvistendahl JJ, Andersen H et al (2000) The effect of bladder outlet obstruction on tissue oxygen tension and blood flow in the pig bladder. BJU Int 85:1109
Pinggera GM, Mitterberger M, Steiner E et al (2008) Association of lower urinary tract symptoms and chronic ischaemia of the lower urinary tract in elderly women and men: assessment using colour Doppler ultrasonography. BJU Int 102:470
Rossello X, Piñero A, Fernández-Jiménez R et al (2018) Mirabegron, a Clinically Approved β3 Adrenergic Receptor Agonist, Does Not Reduce Infarct Size in a Swine Model of Reperfused Myocardial Infarction. J Cardiovasc Transl Res 11:310
Dehvari N, da Silva Junior ED, Bengtsson T et al (2018) Mirabegron: potential off target effects and uses beyond the bladder. Br J Pharmacol 175:4072
Robinson D, Thiagamoorthy G, Cardozo L (2016) A drug safety evaluation of mirabegron in the management of overactive bladder. Expert Opin Drug Saf 15:689
Alexandre EC, Kiguti LR, Calmasini FB et al (2016) Mirabegron relaxes urethral smooth muscle by a dual mechanism involving β3 -adrenoceptor activation and α1 -adrenoceptor blockade. Br J Pharmacol 173:415
Andersson KE (1999) Pathways for relaxation of detrusor smooth muscle. Adv Exp Med Biol 462:241
Sadananda P, Drake MJ, Paton JF et al (2013) A functional analysis of the influence of β3-adrenoceptors on the rat micturition cycle. J Pharmacol Exp Ther 347:506
Majima T, Matsukawa Y, Funahashi Y et al (2020) The effect of mirabegron on bladder blood flow in a rat model of bladder outlet obstruction. World J Urol 38:2021
Silva I, Costa AF, Moreira S et al (2017) Inhibition of cholinergic neurotransmission by β(3)-adrenoceptors depends on adenosine release and A(1)-receptor activation in human and rat urinary bladders. Am J Physiol Renal Physiol 313:F388
Maki T, Kajioka S, Itsumi M et al (2019) Mirabegron induces relaxant effects via cAMP signaling-dependent and -independent pathways in detrusor smooth muscle. Low Urin Tract Symptoms 11:O209
Su S, Lin J, Liang L et al (2020) The efficacy and safety of mirabegron on overactive bladder induced by benign prostatic hyperplasia in men receiving tamsulosin therapy: A systematic review and meta-analysis. Medicine (Baltimore) 99:e18802
Herschorn S, McVary KT, Cambronero Santos J et al (2021) Mirabegron vs placebo add-on therapy in men with overactive bladder symptoms receiving tamsulosin for underlying benign prostatic hyperplasia: a safety analysis from the randomized, phase 4 PLUS study. Urology 147:235
Tadayyon F, Izadpanahi M, Aali S et al (2012) The effect of sublingual isosorbide dinitrate on acute urinary retention due to benign prostatic hyperplasia. Saudi J Kidney Dis Transpl 23:782
Fusco F, Creta M, De Nunzio C et al (2018) Progressive bladder remodeling due to bladder outlet obstruction: a systematic review of morphological and molecular evidences in humans. BMC Urol 18:15
Holm NR, Horn T, Smedts F et al (2002) Does ultrastructural morphology of human detrusor smooth muscle cells characterize acute urinary retention? J Urol 167:1705
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The authors have no conflicts of interest to disclose.
This study was approved by the Institutional Animal Care and Use Committee (IACUC) of Korea University (Approval number: KOREA-2020–0041-C1), and the animal laboratory guidelines were followed.
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Noh, T.I., Shim, J.S., Kang, S.G. et al. Effects of β3-adrenoceptor agonist on acute urinary retention in a rat model. World J Urol (2021). https://doi.org/10.1007/s00345-021-03774-7
- Acute urinary retention
- Bladder dysfunction