(1) Department Of Urology Shinshu University School Of Medicine, Matsumoto, Japan
Detrusor overactivity induced by cold stress in spontaneously hypertensive rats were could be inhibited with β3 adrenergic receptor agonist and muscarinic receptor antagonist (1). This study determined if combined treatment with β3 adrenergic receptor agonist, mirabegron and muscarinic receptor antagonist, solifenacin could inhibit detrusor overactivity induced by cold stress in diabetic disease rats.
Female 10-week-old Goto-Kakizaki (GK) rats, which were diabetic disease model animals were kept with a high-fat diet for 4 weeks. Prior to three days of cystometric investigations, they were cannulated. Cystometric measurements of the unanesthetized, unrestricted rats were performed at room temperature (RT 27±2℃) to record base lines. The rats were then intravenously administered with combination of 0.1mg/kg mirabegron and 0.1mg/kg solifenacin or vehicle. Ten minutes later, the treated rats were smoothly and gently transferred into cold room to expose low temperature (LT 4±2℃) for 40 minutes. During the exposure, the cystometric measurements were continued. Finally, the rats were returned to RT.
Under RT, micturition parameters of the combination-treated rats did not show any differences compared to the vehicle-treated ones. Just after transfer from RT to LT, the vehicle-treated GKs exhibited detrusor overactivity that decreased voiding interval and bladder capacity. However, treatment with the combination of mirabegron and solifenacine partially inhibited decreases of voiding interval and bladder capacity with the cold stress-induced detrusor overactivity.
This study suggested that the combination of β3 adrenergic receptor agonist and muscarinic receptor antagonist might be able to inhibit the cold stress-induced detrusor overactivity in GKs.