Aims: Statins are widely used to treat dyslipidemia and have been shown to reduce the risk of ischemic heart disease and cerebrovascular disease. The effects of statins on ischemia-induced overactive bladder (OAB) and the associated mechanisms were investigated in a rat model of chronic pelvic ischemia.
Methods: A pelvic ischemia model was created by iliac arterial injury (AI) and a high-fat diet using male Sprague-Dawley rats. Rats were assigned to 3 groups: control group, AI group, and AI + statin group. The control group underwent sham operation and was fed a normal diet. The AI group underwent AI surgery and was fed a high-cholesterol diet. The AI + statin group was administered a statin for 4 weeks. Cystometry was performed for 8 weeks after surgery. Blood flow was evaluated by laser meter. Thickness of the iliac arteries was measured, and microvascular density in the lamina propria was evaluated by immunostaining for CD31. Expressions of inflammatory cytokines in the bladder were measured by real-time PCR.
Results: Cystometry showed a significantly shorter voiding interval and lower bladder capacity in the AI group than in the control group. The AI + statin group showed improvement of these findings. The AI group showed decreased bladder blood flow, increased iliac arterial wall thickening, and decreased microvascular density compared to the control group. Statin administration improved blood flow. Iliac arterial wall thickening was suppressed, and microvascular density was increased by statin administration, though not significantly. Real-time PCR showed significantly higher expressions of inflammatory cytokines (IL-6, IL-8, and TNF-α) in the AI group than in the control group, and IL-6 and IL-8 expressions were lower in the AI + statin group than in the AI group.
Conclusions: The present results suggest that statins are effective in OAB caused by arteriosclerosis and ischemia. The mechanism of their effects involves improved bladder blood flow and decreased bladder inflammation.
Keywords: atherosclerosis; inflammation; lower urinary tract disease; metabolic syndrome; overactive bladder; pelvic ischemia; statin.
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