Neurogenic Function of the Diabetic Rat Bladder: Alteration by Calcium Channel Effectors

Abstract

The in vitro effects of a calcium channel antagonist (nifedipine) and agonist (BAY K8644) on the neurogenic responses of the streptozotocin-induced diabetic rat bladder were investigated. The bladder body and bladder base were studied separately. There were no significant differences in neurogenic responses in diabetic bladder body compared to control body, but the diabetic bladder base demonstrated an increased contractile response at each frequency compared to control base. The rate of contractile response was similar in controls and diabetics but was significantly different between body and base. Although declining with time, contractile responses in the diabetic bladder body and base were increased from control in the absence of extracellular calcium. Differences were found in effects upon maximum responses between diabetic and control tissues treated with nifedipine and BAY K8644. BAY K8644 did not completely reverse the effect of nifedipine on the neurogenic responses in the diabetic bladder body. Effects of diabetes on the bladder body and base are associated with changes in calcium channel activity of bladder smooth muscle.

Cytosol-Free Calcium Concentration in Single Bladder Smooth Muscle Cells from Normal and Diabetic Rats

“…The data suggests that individual smooth muscle cells of diabetic rat bladder responded to car- 96 Qi/Curlev/Belis Cytosol-Free Calcium in Diabetic Rat Bladder bachol stimulation similarly to that of, if not more than, the control cells. However, dia betic bladders do not contract as well as nor mal bladders [7], One explanation may be that the diabetic bladder smooth muscle cells are qualitatively no different from the non diabetic bladder smooth muscle cells, but the relative quantity of smooth muscle cells in diabetic bladder decreases due to an increase in nonmuscle cells. This may lead to enlarge ment of the bladder and cystopathy.…”

“…Diabetes mellitus produces chronic effects on the urinary bladder leading to increased capacity, decreased contractility and de muscle contractile responses to neurogenic stimulation develop with diabetes and are ac companied by altered responses to calcium channel agonists and antagonists [7], Many physiological stimuli regulate cell function by increasing cytosol calcium con centration [8], An important role of calcium is the mediation of smooth muscle contraction. The increase in intracellular calcium during bladder smooth muscle contraction occurs by release of intracellular calcium stores from the sarcoplasmic reticulum and the influx of cal cium from the extracellular medium [9].…”

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“…In two other studies by Longhurst and Belis (1986) and Ichiyanagi et al (2002) a decrease in contractile force in the diabetic urinary bladder tissue was observed in comparison to the controls. 6,12 No clear reason for the discrepancies in published results has been ascertained, however, it is thought a poor or a complete lack of standardization in the contractile force generated may be to blame. 5 In addition, discrepancies may arise due to inadequate experimental protocols i.e.…”

“…Belis et al (1997), theorise that the difference in contractile responses in diabetics compared to control is due to increased calcium (Ca 2+ ) channel activity but in 2000, Waring and Wendt found no supporting evidence and postulate the difference was due to increased Ca 2+ sensitivity.…”

Comparison of Computerized Cystometry/Micturition and Contractile Responses of the Diabetic Rat Bladder

“…Curlcy/Wagner/Murtv/Belis Diabetic Rat Bladder Function Currulative volume infused (ml) (n > 12 for each group) [9], Weights of diabetic and control strips were not significantly different. Contrac tile responses were elicited as previously described in an organ bath [9.10].…”