The effects of chronic hyperlipidemia on bladder function in myocardial infarction‐prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits

Abstract

Lower urinary tract symptoms (LUTS) are common in the aging population. LUTS cause profoundly negative impacts on their quality of life. Pathophysiology of LUTS is multifactorial, and recently, bladder ischemia and metabolic syndrome have been suggested as etiological factors. To evaluate chronic hyperlipidemia on bladder function, we examined the functional and histological changes of the bladder in myocardial infarction-prone Watanabe Heritable Hyperlipidemic (WHHLMI) rabbits. 20- to 24-month-old WHHLMI rabbits and age- and sex-matched control rabbits were prepared. Bladder functions were evaluated using cystometrograms and functional experiments with isolated bladder specimens. Histological studies of bladder and internal iliac arteries were performed with hematoxylin and eosin staining. The bladder was also stained immunohistochemically with mouse monoclonal S-100 antibodies and sheep polyclonal calcitonin gene-related peptide (CGRP) antibodies. In cystometric examination, WHHLMI rabbits showed significantly shorter micturition interval, smaller voided volume with non-voiding contractions, and lower micturition pressure, as compared to control. The functional experiments showed that carbachol- and electrical field stimulation-induced contractions were significantly decreased in WHHLMI rabbits than those in control. In WHHLMI rabbits, cross-sections of internal iliac arteries showed significant atherosclerosis and thickening of media. Bladder showed thinner urothelium and decreased smooth muscle area in WHHLMI rabbits, as compared to control. WHHLMI rabbits showed a significant decrease in S-100 protein positive neurons, and an increased number of CGRP positive neurons. This study demonstrated that WHHLMI rabbits showed detrusor overactivity with decreased detrusor contraction. It is suggested that chronic hyperlipidemia contributes to the bladder dysfunction.