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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Mirabegron elicits rat corpus cavernosum relaxation and increases in vivo erectile response

Full text
Author(s):
de Oliveira, Mariana G. [1] ; Rojas-Moscoso, Julio Alejandro [1] ; Bertollotto, Gabriela M. [1] ; Candido, Tuany Z. [1] ; Kiguti, Luiz Ricardo de A. [1] ; Pupo, Andre S. [2] ; Antunes, Edson [1] ; De Nucci, Gilberto [1] ; Monica, Fabiola Z. [1]
Total Authors: 9
Affiliation:
[1] Univ Estadual Campinas, Fac Med Sci, Dept Pharmacol, UNICAMP, BR-13083881 Campinas, SP - Brazil
[2] Sao Paulo State Univ UNESP, Inst Biosci, Dept Pharmacol, Sao Paulo, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: European Journal of Pharmacology; v. 858, SEP 5 2019.
Web of Science Citations: 1
Abstract

Mirabegron is the first beta 3-adrenoceptor agonist approved on the market and may offer beneficial pharmacological action in patients with overactive bladder and erectile dysfunction. Here, we further investigate the mechanisms by which mirabegron induces rat corpus cavernosum (CC) relaxation. Adult male Wistar rats were used. The CC were isolated for in vitro functional assays and beta-adrenoceptors subtypes mRNA expression evaluation. Animals were treated orally with mirabegron (30 mg/kg, 3 h), tadalafil (10 mg/kg, 3 h) or both for intracavernous pressure (ICP). Intracellular levels of cAMP and cGMP were also determined. The beta 1-, beta 2- and beta 3-adrenoceptors subtypes were expressed in rat CC. Mirabegron produced concentration-dependent CC relaxations that were unaffected by the beta 1-, beta 2- or beta 3-adrenoceptor antagonists atenolol (1 mu M), ICI-118,551 (1 mu M) and L748,337 (10 mu M), respectively. Mirabegron-induced relaxations were not affected by the phosphodiesterase type 4 inhibitor, rolipram, or the adenylyl cyclase selective inhibitor, SQ 22,536. Potassium channel-or calcium influx-blockade are not involved in mirabegron-induced relaxations. In contrast, mirabegron produced rightward shifts in the contractile response induced by the alpha 1-adrenoceptor agonist, phenylephrine. Finally, cavernous nerve stimulation caused frequency-dependent ICP increases, which were significantly increased in rats treated with mirabegron in a similar degree of tadalafil-treated rat, without promoting a significant cAMP or cGMP accumulation. Together, our results demonstrate that mirabegron induced CC relaxation through alpha 1-adrenoceptor blockade. Care should be taken to translate the effect of mirabegron into the clinic, especially when using rat as an animal model of erectile dysfunction. (AU)

FAPESP's process: 18/09765-3 - Voiding and prostatic dysfunction in middle-aged rats and obese mice: focus on NADPH oxidase (NOX)
Grantee:Mariana Gonçalves de Oliveira Taranto
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 13/13907-4 - Evaluation of the effects of opiates agonists in isolated corpus cavernosum from rabbit and rat: does opiate system have role on erectile function?
Grantee:Gilberto de Nucci
Support Opportunities: Regular Research Grants
FAPESP's process: 17/15175-1 - Modulation of soluble guanylate cyclase and the intracellular levels of cyclic nucleotides in the lower urinary tract and prostate
Grantee:Edson Antunes
Support Opportunities: Research Projects - Thematic Grants