Cold stress‐induced bladder overactivity in type 2 diabetic mellitus rats is mitigated by the combination of a M₃‐muscarinic antagonist and a β₃‐adrenergic agonist

This is the authors' abstract. We don't add key points for this paper.

Objectives Goto‐Kakizaki (GK) rats with type 2 diabetes mellitus respond to low temperature (LT) environments with bladder overactivity, including increased voiding frequency and decreased voiding interval and micturition volume. We determined if bladder overactivity could be inhibited by treatment with the combination of a M 3 ‐muscarinic receptor antagonist and a β 3 ‐adrenergic receptor agonist. Methods Ten‐week‐old female GK rats were fed a high‐fat diet for 4 weeks. Cystometric investigations were conducted at room temperature (RT, 27 ± 2°C). The rats were then intraperitoneally administered the vehicle , the M 3 ‐muscarinic receptor antagonist solifenacin, the β 3 ‐adrenergic agonist mirabegron, or a combination of solifenacin and mirabegron. Ten minutes after the administrations, the rats were transferred to the LT environment (4 ± 2°C), where the cystometric measurements were continued. The expressions of both M 3 ‐muscarinic and β 3 ‐adrenergic receptors were investigated. Results After transfer from RT to LT, both voiding interval and bladder capacity of the vehicle‐, solifenacin‐, or mirabegron‐treated rats were significantly decreased. However, the combination of solifenacin and mirabegron significantly mitigated the bladder overactivity. While both M 3 ‐muscarinic and β 3 ‐adrenergic receptors were detected, the expression of M 3 ‐muscarinic receptor mRNA was significantly higher than that of β 3 ‐adrenergic receptor mRNA. Conclusions The cold stress‐induced bladder overactivity was not improved by either the M 3 ‐muscarinic receptor antagonist or the β 3 ‐adrenergic receptor agonist alone. However, the combined treatment mitigated the cold stress responses. Combined therapy with M 3 ‐muscarinic antagonists and β 3 ‐adrenergic agonists could reduce side effects and improve the quality of life for diabetic patients with bladder overactivity.