Nicorandil ameliorates hypertension-related bladder dysfunction in the rat

作者：Saito Motoaki^*; Ohmasa Fumiya; Tsounapi Panagiota; Inoue Seiya; Dimitriadis Fotios; Kinoshita Yukako; Satoh Keisuke

来源：Neurourology and Urodynamics, 2012, 31(5): 695-701.

DOI：10.1002/nau.21213

• KATP channel
• nerve growth factor
• nicorandil ameliorates hypertension-related detrusor overactivity in the rat
• spontaneously hypertensive rat (SHR)

Aims There is increasing evidence that ischemia is one of the main etiology in overactive bladder (OAB), and that nicorandil prevents OAB. We investigated the effect of nicorandil on hypertension-related bladder dysfunction in spontaneously hypertensive rats (SHRs). Methods Twelve-week-old SHRs received six-weeks treatment with nicorandil (0, 3, or 10?mg/kg, i.p. every day). Wistar rats were used for normotensive controls. Six weeks after nicorandil treatment, the bladder blood flow was estimated by hydrogen clearance method, and the bladder functions were estimated by voiding behavior studies and functional studies. Tissue levels of nerve growth factor (NGF) were measured by ELISA method. Furthermore, the participation levels of KATP channel pores were investigated by real-time PCR. Results SHRs showed significant increases in blood pressure, micturition frequency, tissue levels of NGF and expressions of both KIR6.1 and KIR6.2 mRNAs, and a significant decrease in the bladder blood flow. The carbachol-induced contractile responses were similar in all groups. Although both doses of nicorandil failed to decrease the blood pressure, nicorandil significantly decreased the micturition frequency, tissue levels of NGF and increased the bladder blood flow in a dose dependent manner. The expressions of KIR6.1 and KIR6.2 mRNAs were slightly up-regulated by the low dose of nicorandil, whereas the high dose of nicorandil significantly up-regulated those expressions compared to non-treated SHRs. Conclusions These data indicate that nicorandil prevents hypertension-related bladder dysfunction in the SHR, which may be related to its effect on the increased blood flow in the bladder. Neurourol. Urodynam. 31:695701, 2012.

• 出版日期2012-6