ROLE OF SUBSTRATES IN THE MAINTENANCE OF CONTRACTILITY OF THE RABBIT URINARY-BLADDER

Recent studies have shown that muscarinic stimulation causes an increase in the breakdown of glucose and glycogen leading to an increase in lactate and CO2 production and a decrease in the ratio of NADH/NAD. Similar studies using palmitate as substrate showed that bethanechol did not change the rate of palmitate oxidation. Using both isolated strips of rabbit bladder dome, and the rabbit in vitro whole-bladder model, the present study compares the ability of glucose, pyruvate, palmitate, succinate and malate to support contraction and correlates the results with the intracellular concentration of high-energy phosphates. The results can be summarized as follows. In the absence of substrate, the peak response of muscle strips to field stimulation (32 Hz, 80 V, 1 ms) decreased progressively with time to 85% of the initial response at 60 min and 72% at 160 min. In contrast, the plateau phase of the response decreased to 45 and 23% of the initial response at 60 and 160 min, respectively. When glucose was present in the incubation medium, the peak and plateau tensions were 86 and 73% of the initial values at 160 min. Similar experiments with pyruvate as substrate showed that at 160 min both peak and plateau were elevated above initial values (peak = 119%; plateau = 123%). In the presence of palmitate, succinate or malate, the peak and plateau tensions decreased with time at a similar rate as in the absence of substrate. The reduction in tissue content of pre-formed high energy phosphates was similar for zero substrate and when palmitate, succinate or malate were present in the bath. At the end of 160-min incubation, the ability of the in vitro whole bladder to empty following field stimulation was reduced by 95% in the absence of substrate or in the presence of palmitate, succinate or malate compared to 25% in the presence of glucose or pyruvate. Thus, the ability to empty was suppressed to a much greater extent by substrate deprivation than the phasic increase in intravesical pressure. These results indicate that phasic force generation and the ability to maintain tension may have separate metabolic properties. The phasic response being mediated by high energy phosphates, while the tonic phase of the response is linked to aerobic, oxidative metabolism.