Energetics of detrusor contraction: Effects of outlet obstruction

Abstract

AbstractPrevious studies demonstrated that the ability of the urinary bladder to empty was impaired after mild outlet obstruction. One contributing factor may be the derangement of intracellular energy metabolism. The primary objective of the current study is to examine the energentics of detrusor contraction in normal and obstructed rabbit urinary bladders. Mild bladder outlet obstruction was induced in male rabbits; after 2 weeks of partial outlet obstruction, three muscle strips were isolated from the bladder body of each obstructed and control rabbit. One of these strips was frozen at unstimulated state, while the remaining two strips were stimulated with 500 m̈M bethanechol and frozen separately either at maximal phasic (peak) contraction or during plateau (tonic) contraction. Tissue content of adenine nucleotides (ATP, ADP, AMP), NAD (nicotinamide adenine dinucleotide), creatine, and creatine phosphate were determined using reverse phase high performance liquid chromatography (HPLC).The results can be summarized as follows: 1) The tissue content of creatine phosphate of the unstimulated control bladder was significantly higher than in the obstructed bladders. The tissue content of all other compounds were similar. 2) In the normal bladder strips, bethanechol stimulation induced a significant net decrease only in the tissue content of creatine phosphate during the plateau phase of contraction. 3) In the obstructed bladder strips, bethanechol stimulation induced a decrease in both ATP and creatine phosphate during the plateau phase of the response. The decrease in creatine phosphate was of a significantly greater magnitude than the decrease of creatine phosphate observed in normal strips. In addition, AMP content was significantly increased during both peak and plateau contraction.These observations show that mild bladder outlet obstruction results in changes in the energy metabolism of detrusor contraction, which indicates that the obstructed bladder is unable to maintain proper tissue levels of high energy phosphates which are necessary for adequate detrusor contraction.