Effects of Chronic Hyperlipidemia on Lower Urinary Tract Function—Bladder Dysfunction in Myocardial Infarction‐Prone Watanabe Heritable Hyperlipidemic Rabbits

To evaluate the effects of chronic hyperlipidemia on bladder function, we examined the functional and histological changes of the bladder in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHL-MI) rabbits. Two age groups of WHHL-MI rabbits (6-12 months old, young WHHL-MI rabbits; and 20-24 months old, old WHHL-MI rabbits group) and the sex- and age-matched control rabbits were prepared. Bladder functions were evaluated using frequency volume charts and cystometrograms, and functional experiments using isolated bladder specimens. Histological studies of bladder were performed with HE staining and immunohistochemical staining with mouse monoclonal S-100 protein antibodies and sheep polyclonal calcitonin gene-related peptide (CGRP) antibodies. In cystometrograms, it has been demonstrated that WHHL-MI rabbits showed significantly shorter micturition interval, smaller voided volume with non-voiding contractions compared to control. There was no significant difference in voiding pressure between young WHHL-MI and control rabbits. However, old WHHL-MI rabbits showed a lower voiding pressure than control rabbits. The functional experiments revealed that carbachol- and electrical field stimulation (EFS)-induced contractile responses of isolated bladder strips were significantly increased in young WHHL-MI rabbits than in control rabbits. However, in the bladder strips of old WHHL-MI rabbits, decreased responses to carbachol and EFS were observed. In WHHL-MI rabbits, bladder urothelium became thinner, smooth muscle area decreased and connective tissue area increased gradually with aging. A significant decrease in S-100 protein-positive neurons, and an increased number of CGRP-positive neurons were observed in both young and old WHHL-MI rabbits. The data demonstrated that there were differences in bladder dysfunction between young and old WHHL-MI rabbits. Old WHHL-MI rabbits showed detrusor hyperactivity with impaired contraction. This study may demonstrate the developmental mechanism of bladder dysfunction in chronic hyperlipidemia.