Objectives To investigate the effects of an alpha1‐adrenoceptor antagonist, silodosin, or a phosphodiesterase type 5 inhibitor, tadalafil, on bladder overactivity in spontaneously hypertensive rats. Methods Twelve‐week‐old male spontaneously hypertensive rats were perorally administered silodosin (100 µg/kg), tadalafil (2 or 10 mg/kg) or vehicle once daily for 6 weeks. Wistar rats were used as normotensive controls and were treated with the vehicle. At 18‐weeks‐old, the effects of silodosin or tadalafil on blood pressure, bladder blood flow, urodynamic parameters (i.e. micturition frequency, urine output, inter‐contraction interval, maximum voiding pressure, single voided volume and post‐voiding residual urine volume), and bladder tissue levels of malondialdehyde, interleukin‐6 and tumor necrosis factor‐alpha were measured. Results A significant increase in blood pressure, micturition frequency and bladder tissue levels of malondialdehyde, interleukin‐6 and tumor necrosis factor‐alpha was noted in spontaneously hypertensive rats. The single voided volume, bladder capacity and bladder blood flow were significantly lower in the spontaneously hypertensive rats than in the Wistar rats. Treatment with silodosin and the higher dose of tadalafil improved the urodynamic parameters, bladder blood flow and bladder tissue levels of malondialdehyde in the spontaneously hypertensive rats without affecting the blood pressure and bladder tissue levels of interleukin‐6 and tumor necrosis factor‐alpha. Conclusions Treatment with silodosin or tadalafil might improve hypertension‐related bladder overactivity, as shown in spontaneously hypertensive rats through an improvement in the bladder blood flow and bladder tissue levels of oxidative stress.

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Aim Brain nitric oxide (NO) have been reported in regulation of the sympatho‐adrenomedullary system, which can affect voiding and storage functions. Therefore, we investigated effects of intracerebroventricularly (icv) administered 3‐(4‐morpholinyl)sydnonimine, hydrochloride (SIN‐1) (NO donor) on the micturition reflex, focusing on their dependence on the sympatho‐adrenomedullary system and on brain N‐methyl‐D‐aspartate (NMDA) and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA) receptors in urethane‐anesthetized (0.8 g/kg, ip) male Wistar rats. Methods Plasma noradrenaline and adrenaline were measured just before and 5 minutes after SIN‐1 administration. Evaluation of urodynamic parameters was started 1 hour before SIN‐1 administration or intracerebroventricular pretreatment with other drugs. Results SIN‐1 (100 and 250 µg/animal) elevated plasma adrenaline and reduced intercontraction interval ([ICI] values; 110.5% [SIN‐1, 0 µg] and 54.9% [SIN‐1, 250 µg] during 15 minutes after SIN‐1 administration [P < .05; η2 = 0.59]) without affecting plasma noradrenaline or maximal voiding pressure. SIN‐1 (250 µg/animal) reduced single‐voided volume and bladder capacity without affecting post‐voiding residual volume. The SIN‐1 (250 µg/animal)‐induced adrenaline elevation and ICI reduction were attenuated by 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl‐3‐oxide, sodium salt (carboxy‐PTIO) (NO scavenger, icv) (ICI values; 44.7% [vehicle + SIN‐1] and 77.5% [carboxy‐PTIO + SIN‐1] during 15 minutes after SIN‐1 administration [P < .05; η2 = 0.51]). Acute bilateral adrenalectomy abolished SIN‐1‐induced adrenaline elevation, while showed no effect on the SIN‐1‐induced ICI reduction. The ICI reduction was attenuated by MK‐801 (NMDA receptor antagonist, icv) (ICI values; 47.0% [vehicle + SIN‐1] and 87.6% [MK‐801 + SIN‐1] during 15 minutes after SIN‐1 administration [P < .05; η2 = 0.61]), but not by DNQX (AMPA receptor antagonist, icv). Conclusion Brain NO is involved in facilitation of the rat micturition reflex through brain NMDA receptors, independently of the sympatho‐adrenomedullary outflow modulation.

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Aims The goal of this study was to test whether central corticotropin‐releasing factor (CRF) was involved in angiotensin II (Ang II) and Ang II type 1 (AT1) receptor‐mediated facilitation of micturition reflex and to investigate whether peripherally administered telmisartan, AT1 receptor antagonist, suppresses the central Ang II‐induced facilitation of micturition reflex in rats. Methods Urethane anesthetized male Wistar rats were placed under continuous cystometry before and after intracerebroventricular administration of each drug. Rats were intracerebroventricularly administered telmisartan (AT1 receptor antagonist), CP154526 (CRF1 receptor antagonist), or K41498 (CRF2 receptor antagonist) 30 minutes before intracerebroventricular administration of Ang II. Some male Wistar rats were perorally pretreated with either vehicle, AT1 receptor antagonist telmisartan or valsartan, once daily for 8 days, then measured blood pressure. Thereafter, Ang II was intracerebroventricularly administered for continuous cystometry. Results Intracerebroventricularly administered telmisartan or CP154526 dose‐dependently suppressed the central Ang II‐induced intercontraction interval (ICI) reduction. In contrast, intracerebroventricularly administered K41498 did not affect the central Ang II‐induced response compared to vehicle pretreatment. Peripherally administered telmisartan but not valsartan suppressed the central Ang II‐induced ICI reduction in rats compared to vehicle administration without altering blood pressure. Conclusions Central Ang II induced facilitation of the micturition reflex through AT1 and CRF1 receptors. Peripherally administered telmisartan suppressed central Ang II‐induced facilitation of micturition reflex.