Effects of a new β3-adrenoceptor agonist, vibegron, on neurogenic bladder dysfunction and remodeling in mice with spinal cord injury

被引：13

作者：

Gotoh, Daisuke ^{[1
,2
]}

Shimizu, Nobutaka ^{[1
,3
]}

Wada, Naoki ^{[1
]}

Kadekawa, Katsumi ^{[1
]}

Saito, Tetsuichi ^{[1
]}

Mizoguchi, Shinsuke ^{[1
]}

Morizawa, Yosuke ^{[2
]}

Hori, Shunta ^{[2
]}

Miyake, Makito ^{[2
]}

Torimoto, Kazumasa ^{[2
]}

de Groat, William C. ^{[4
]}

Fujimoto, Kiyohide ^{[2
]}

Yoshimura, Naoki ^{[1
,4
]}

机构：

[1] Univ Pittsburgh, Dept Urol, Pittsburgh, PA 15213 USA

[2] Nara Med Univ, Dept Urol, Kashihara, Nara, Japan

[3] Kindai Univ, Fac Med, Dept Urol, Osaka, Japan

[4] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA

来源：

NEUROUROLOGY AND URODYNAMICS | 2020年 / 39卷 / 08期

关键词：

detrusor overactivity; mice; spinal cord injury; urodynamics; vibegron; URINARY-BLADDER; NEUROTROPHIC FACTOR; AFFERENT ACTIVITY; REFLEX PATHWAYS; MESSENGER-RNA; RATS; MIRABEGRON; INHIBITION; ANTAGONIST; EXPRESSION;

D O I：

10.1002/nau.24486

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Aims To examine vibegron effects on lower urinary tract dysfunction (LUTD) in mice with spinal cord injury (SCI). Methods Female mice underwent Th8-9 spinal cord transection and were orally administered vehicle or vibegron after SCI. We evaluated urodynamic parameters at 4 weeks after SCI with or without vibegron. Fibrosis- and ischemia-related messenger RNA (mRNA) and protein levels of collagen and elastin were measured in bladders of vehicle- and vibegron-treated SCI mice, and spinal intact mice. Results Non-voiding contractions (NVCs) were significantly fewer (15.3 +/- 8.9 vs 29.7 +/- 11.4 contractions;P < .05) and the time to the first NVC was significantly longer (1488.0 +/- 409.5 vs 782.7 +/- 399.7 seconds;P < .01) in vibegron-treated SCI mice vs vehicle-treated SCI mice. mRNAs levels of collagen types 1 and 3, transforming growth factor-beta 1 (TGF-beta 1), and hypoxia-inducible factor-1 alpha (HIF-1 alpha) were significantly upregulated in vehicle-treated SCI mice compared with spinal intact and vibegron-treated SCI mice (Col 1: 3.5 vs 1.0 and 2.0-fold;P < .01 andP < .05, Col 3: 2.1 vs 1.0 and 1.2-fold;P < .01 andP < .05, TGF-beta 1: 1.2 vs 1.0 and 0.9-fold;P < .05 andP < .05, HIF-1 alpha: 1.4 vs 1.0 and 1.0-fold;P < .05 andP < .01). Total collagen and elastin protein levels in vehicle- and vibegron-treated SCI mice did not differ. Conclusions Vibegron reduced NVCs, delayed the first NVC, and improved collagen types 1 and 3, TGF-beta 1, and HIF-1 alpha mRNA expression in SCI mice. Vibegron might be effective for SCI-induced LUTD.

引用

页码：2120 / 2127

页数：8

共 28 条

[1]

Agrawal M, 2015, J SPINAL CORD MED, V38, P128, DOI 10.1179/2045772313Y.0000000136

[2] Effects of L-Arginine, Mirabegron, and Oxybutynin on the Primary Bladder Afferent Nerve Activities Synchronized With Reflexic, Rhythmic Bladder Contractions in the Rat [J].

Aizawa, Naoki ;

Homma, Yukio ;

Igawa, Yasuhiko .

NEUROUROLOGY AND URODYNAMICS, 2015, 34 (04) :368-374

[3] Effects of Mirabegron, a Novel β3-Adrenoceptor Agonist, on Primary Bladder Afferent Activity and Bladder Microcontractions in Rats Compared With the Effects of Oxybutynin [J].

Aizawa, Naoki ;

Homma, Yukio ;

Igawa, Yasuhiko .

EUROPEAN UROLOGY, 2012, 62 (06) :1165-1173

[4] Plasticity in reflex pathways to the lower urinary tract following spinal cord injury [J].

de Groat, William C. ;

Yoshimura, Naoki .

EXPERIMENTAL NEUROLOGY, 2012, 235 (01) :123-132

[5] Changes in Afferent Activity After Spinal Cord Injury [J].

de Groat, William C. ;

Yoshimura, Naoki .

NEUROUROLOGY AND URODYNAMICS, 2010, 29 (01) :63-76

[6] Mirabegron elicits rat corpus cavernosum relaxation and increases in vivo erectile response [J].

de Oliveira, Mariana G. ;

Rojas-Moscoso, Julio Alejandro ;

Bertollotto, Gabriela M. ;

Candido, Tuany Z. ;

Kiguti, Luiz Ricardo de A. ;

Pupo, Andre S. ;

Antunes, Edson ;

De Nucci, Gilberto ;

Monica, Fabiola Z. .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2019, 858

[7] β3-Adrenoceptors in the normal and diseased urinary bladder-What are the open questions? [J].

Igawa, Yasuhiko ;

Aizawa, Naoki ;

Michel, Martin C. .

BRITISH JOURNAL OF PHARMACOLOGY, 2019, 176 (14) :2525-2538

[8] The role of capsaicin-sensitive C-fiber afferent pathways in the control of micturition in spinal-intact and spinal cord-injured mice [J].

Kadekawa, Katsumi ;

Majima, Tsuyoshi ;

Shimizu, Takahiro ;

Wada, Naoki ;

de Groat, William C. ;

Kanai, Anthony J. ;

Goto, Momokazu ;

Yoshiyama, Mitsuharu ;

Sugaya, Kimio ;

Yoshimura, Naoki .

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2017, 313 (03) :F796-F804

[9] Effects of an alpha1A/D-adrenoceptor antagonist, naftopidil, and a phosphodiesterase type 5 inhibitor, tadalafil, on urinary bladder remodeling in rats with spinal cord injury [J].

Kadekawa, Katsumi ;

Majima, Tsuyoshi ;

Kawamorita, Naoki ;

Okada, Hiroki ;

Yoshizawa, Tsuyoshi ;

Mori, Kenichi ;

Tyagi, Pradeep ;

Sugaya, Kimio ;

Yoshimura, Naoki .

NEUROUROLOGY AND URODYNAMICS, 2017, 36 (06) :1488-1495

[10] Characterization of bladder and external urethral activity in nice with or without spinal cord injury-a comparison study with rats [J].

Kadekawa, Katsumi ;

Yoshimura, Naoki ;

Majima, Tsuyoshi ;

Wada, Naoki ;

Shimizu, Takahiro ;

Birder, Lori A. ;

Kanai, Anthony J. ;

de Groat, William C. ;

Sugaya, Kimio ;

Yoshiyama, Mitsuharu .

AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2016, 310 (08) :R752-R758

← 1 2 3 →