Alpha1A-adrenoceptor antagonist improves underactive bladder associated with diabetic cystopathy via bladder blood flow in rats

Abstract

Background: Patients with diabetes experience lower urinary tract symptoms. Cystopathy may evolve into underactive bladder (UAB), depending on the degree and duration of the symptoms. In the present study, we aimed to investigate the effects of silodosin, an alpha 1A -adrenoceptor (AR) antagonist, on UAB in a rat model of diabetes mellitus (DM). Methods: Female Sprague-Dawley rats (6 weeks old) were administered streptozotocin (STZ) (50 mg/kg, i.v.) to establish a DM model. One week after STZ administration, vehicle or silodosin (0.3 or 1 mg/kg/day) was delivered subcutaneously through an osmotic pump. Nine weeks after STZ administration (8 weeks after drug treatment), a catheter was implanted into the bladder under urethane anesthesia. After the measurement of emptied bladder blood flow (BBF), saline was continuously infused into the bladder and intravesical pressure and micturition volume were measured. In another experiment, the bladder was isolated and nerve markers were quantified. Results: A cystometrogram showed that bladder capacity (BC), residual volume (RV), and bladder extension (BC/ bladder weight) increased by 7.43, 10.47, and 3.59 times, respectively, in vehicle rats in comparison with normal rats. These findings suggested the occurrence of UAB-like symptoms in this model. Silodosin (1 mg/kg/day) inhibited the increase in BC and RV by 49.0% and 46.8%, respectively, and caused a decrease in BBF of approximately 25.5% (when the difference between normal and vehicle was set as 100%) in STZ rats. The nerve marker expression levels tended to be decreased in the bladders of STZ rats and these effects were ameliorated by silodosin. Conclusions: The STZ rats showed increased bladder extension and RV, symptoms that were suggestive of UAB, and these symptoms were ameliorated by silodosin. These results suggested that the alpha 1A -AR antagonist would be useful for the prevention or treatment of UAB.

Therapeutic effect of integrin-linked kinase gene-modified bone marrow-derived mesenchymal stem cells for streptozotocin-induced diabetic cystopathy in a rat model

“…However, contrary to our current concept about DCP, some studies have revealed that hyperglycemia does not result in a loss of parasympathetic sensory nerve fibers in the bladder [7]. Therefore, around the world, there has been considerable interest in improving underactive bladder associated with DCP via bladder blood flow [8].…”

Effects of tadalafil versus silodosin on voiding function in male patients with non‐neurogenic detrusor underactivity: A comparative study using propensity score matching

“…Additionally, Yonekubo et al . reported that silodosin improved voiding efficiency by increasing BBF in a diabetic cystopathy‐associated DU rat model 19 . Goi et al .…”

“…8,9,[16][17][18] Additionally, Yonekubo et al reported that silodosin improved voiding efficiency by increasing BBF in a diabetic cystopathy-associated DU rat model. 19 Goi et al reported that silodosin prevented the decrease in nerve distribution of the bladder and the increase in nerve growth factor expression by improving BBF in an atherosclerosis rat model, and ameliorated detrusor contractile function. 20 Tadalafil has also been reported to improve BBF in not only a BOO rat model, but also a DU rat model induced by diabetes mellitus.…”

Grape seed proanthocyanidin extract alleviates urethral dysfunction in diabetic rats through modulating the NO‑cGMP pathway

“…To date, the majority of studies examining DM complications have focused on the pathogenesis and management of diabetic cystopathy, one of the most common complications of DM (1,2). Diabetic cystopathy is considered to be a manifestation of polyneuropathy, involving sensory and autonomic nerve fibers 1 (3).…”