Factors underlying the increased sensitivity to field stimulation of urinary bladder strips from streptozotocin‐induced diabetic rats

Abstract

The responses of bladder strips from control, streptozotocin‐diabetic, and sucrose‐drinking rats to electrical field stimulation were investigated. Sucrose‐drinking rats were included as additional controls because they have enlarged bladders as a result of non‐diabetic diuresis. Bladder strips from diabetic rats developed more spontaneous activity than those from the two control groups. Indomethacin reduced the amplitude and frequency of spontaneous contractions suggesting that they resulted from endogenous prostaglandin formation. Tetrodotoxin (TTX) had little effect, while α,β‐methylene ATP caused increases in spontaneous activity. Bladder strips from diabetic rats responded to field stimulation with greater contractions than controls in the absence of antagonists as well as in the presence of atropine and α,β‐methylene ATP. Increasing TTX concentrations caused a step‐wise depression of the contractile response to electrical stimulation which was not affected by preincubation with either atropine or α,β‐methylene ATP. Atropine and indomethacin had no effect on stength‐duration curves constructed to measure threshold contractile responses to five pulses stimulation. The curves were shifted to the right by both TTX and α,β‐methylene ATP, indicating that the responses were neurogenic in nature and at least partially, the result of stimulation of P2‐purinoceptors. In the absence of drugs, bladder strips from diabetics responded at lower voltages and pulse widths than those of control and sucrose‐drinking rats, suggesting that they were more excitable. The response curve of bladder strips from diabetics to field stimulation at increasing voltage was shifted upwards and to the left compared to strips from control or sucrose‐drinking rats. Bladder strips from diabetics responded to stimulation at increasing pulse width with greater responses than those from control or sucrose‐drinking rats. At 1.0 ms pulse width, the TTX‐resistant response of strips from diabetic rats was still greater than that of the other groups, indicating that a myogenic component was also involved. The data suggest that bladder strips from diabetic rats are more excitable than those of control or sucrose‐drinking rats. This may result from diabetes‐induced decreases in bladder lipid or other membrane changes, and/or be a result of partial depolarization, perhaps related to diabetic neuropathy. 1994 British Pharmacological Society