Increased expression of heat shock protein 20 and decreased contractile stress in obstructed rat bladder

Bladder outlet obstruction induces detrusor hypertrophy and it can eventually lead to decreased bladder smooth muscle contractility. Heat shock protein 20 is the proposed mediator of force suppression in vascular smooth muscle. We investigated whether heat shock protein 20 could also mediate the decreased contractility observed in partially obstructed rat bladders.

Female Wistar rats (Harlan Laboratories, Indianapolis, Indiana) were randomized to partial urethral ligation or sham ligation. After 3 weeks the rats were sacrificed, and the bladders were harvested, frozen, homogenized and analyzed for heat shock protein 20 content by Western blot immunoreactivity. The content of myosin regulatory light chain, a constitutively expressed protein, was determined as a control. Bladder smooth muscle strips were dissected from some rats and mounted for force generation measurement.

At cystectomy obstructed bladders were significantly heavier and had more residual urine compared to sham operated bladders. Heat shock protein 20 immunoreactivity was significantly increased a mean +/- 1 SEM of 1.9 +/- 0.3-fold in obstructed vs sham operated bladders. Control protein myosin regulatory light chain immunoreactivity did not significantly differ in obstructed and sham operated bladders. Maximal stress, that is force per cross-sectional area, was significantly decreased in obstructed vs sham operated bladders. Human bladder was found to express immunoreactive heat shock protein 20.

We noted that partially obstructed rat bladders 1) express higher levels of heat shock protein 20 and 2) generate less stress than sham operated bladders. These data suggest the possibility that heat shock protein 20 over expression could at least partially mediate the decreased contractile activity observed with partial bladder outlet obstruction. The mechanism for increased heat shock protein 20 expression is unknown but it may involve increased mechanical stress or hypoxia from urethral obstruction. Human bladder expressed immunoreactive heat shock protein 20, suggesting that a similar mechanism could potentially occur in humans. If confirmed in humans, patients with clinical conditions that result in detrusor hypocontractility could potentially benefit from pharmacological interventions aimed at inhibiting heat shock protein 20.