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Lipid signaling changes in smooth muscle remodeling associated with partial urinary bladder outlet obstruction
Author(s) -
LaBelle Edward,
Zderic Stephen,
Delaney Daniel,
Hypolite Joseph,
Wein Alan,
Chacko Samuel
Publication year - 2006
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.20214
Subject(s) - bladder outlet obstruction , muscle hypertrophy , medicine , carbachol , detrusor muscle , endocrinology , urology , urinary bladder , arachidonic acid , overactive bladder , phospholipase a2 , urinary system , chemistry , pathology , stimulation , biochemistry , prostate , enzyme , alternative medicine , cancer
Aims Hypertrophy of the urinary bladder smooth muscle (detrusor) is associated with partial bladder outlet obstruction (PBOO). Hypertrophied detrusor smooth muscle (DSM) reveals altered contractile characteristics. In this study, we analyzed the lipid‐dependent signaling system that includes phospholipase A 2 in PBOO‐induced DSM remodeling and hypertrophy to determine whether the release of arachidonic acid (AA) from phospholipid is altered in the detrusor. Methods Partial bladder outlet obstruction (PBOO) was produced by partial ligation of the urethra in New Zealand white rabbits. Two weeks after the surgery, the bladder function was studied by keeping the rabbits in metabolic cages for 24 hr. Bladders were removed from rabbits that had bladder dysfunction (increased urinary frequency and decreased void volume) and the DSM separated from mucosa and serosa. The isolated smooth muscle was incubated with [ 3 H] AA to equilibrate the cytoplasmic AA. The level of AA release was compared with the level obtained with 2‐week sham‐operated rabbits. Results The rate of AA release was high in DSM from bladders with PBOO‐induced hypertrophy. Carbachol stimulated AA release in control DSM but DSM from obstructed rabbits revealed no further increase from the elevated basal AA release. The half‐maximal concentration of carbachol that was required to stimulate AA release from control samples of detrusor was 35 µM. Conclusions The increased levels of AA release that are observed in this tissue after PBOO indicate the activation of phospholipase A 2 . The finding that carbachol could induce contraction, but not an increase in AA, indicates that the carbachol‐induced contraction in the obstructed bladders is independent of lipid signaling pathways that involve AA. It is possible that the increased rate of arachidonic acid release from obstructed bladders correlates with the enhanced rates of prostaglandin production reported by other investigators from the same tissue. Neurourol. Urodynam. © 2006 Wiley‐Liss, Inc.