Effects Of Berberine On Contractile Responses In The Isolated Urinary Bladder Detrusor Strips Of Diabetic Rats

Objective: To investigate the alteration of contractile responses in the isolated urinary bladder detrusor strips of diabetic rats and the effects of berberine on contractile responses in the isolated urinary bladder detrusor strips of diabetic rats.Methods: Male Sprague-Dawley rats were divided into 3 groups: normal group, sucrose diuretic group and diabetic group. Rats in diabetic group were fasted for 12h before streptozotocin administration (50mg·kg-1 in 1% sodium citrate buffer) by intraperitoneal injection. Rats in normal and diuretic groups received an intraperitoneal injection of 1% sodium citrate buffer instead of streptozotocin, and then the rats in diuretic group were fed with 5% sucrose in drinking water. At the end of 4 weeks, rats of the 3 groups were killed, the bladder was removed and detrusor strips were prepared carefully. Alterations in contractile responses of the isolated rat urinary bladder detrusor strips in the early stage of diabetes onset were observed. Adrenergic, cholinergic and nonadrenergic- noncholinergic (NANC) contractile responses and their transmitter-related contractile responses in the isolated urinary bladder detrusor strips were analyzed. Effects of berberine on the contractile responses to electric field stimulation (EFS), carbachol, KCl and ATP in the isolated urinary bladder detrusor strips of diabetic rats were studied.Results:1 Body weight, bladder wet weight and blood glucose level of the diabetic ratsIn comparison with the body weight of normal or diuretic rats, that of diabetic rats was decreased significantly, and their blood glucose levels on the 3rd day and 28th day after streptozotocin administration were increased significantly. The bladder wet weight (126.12±27.28mg) of diabetic rats was significantly higher than that of normal rats (71.36±12.87mg, P<0.01) and diuretic rats (98.67±11.13mg, P<0.01). The bladder wet weight of diuretic rats was slightly but significantly (P<0.01) higher than that of normal rats. There were epithelial proliferation of the mucosa and the hydropic change or vacuolar degeneration of the cell in the urinary bladder detrusor in the diabetic rats.2 Effects of atropine, prazosin and tetrodotoxin on contractile responses to electric field stimulation in the isolated urinary bladder detrusor strips of the diabetic ratsEFS (1~32Hz) produced reproducible and frequency- dependent contractions in the isolated urinary bladder detrusor strips of the normal and diabetic rats, and the contractions were completely inhibited by 0.1μmol·L-1 tetrodotoxin. The contractile responses to EFS in the isolated urinary bladder detrusor strips of diabetic rats were significantly smaller than those of the normal rats (P<0.01). Atropine at 1μmol·L-1 significantly inhibited EFS-induced contractile responses in the isolated urinary bladder detrusor strips of the normal and diabetic rats, and maximal inhibition on the contractile responses to EFS at 32Hz in normal and diabetic rats was 40% and 25%, respectively. Prazosin at 1μmol·L-1 failed to affect EFS-induced contractile responses in the isolated urinary bladder detrusor strips (P>0.05).3 Effects of berberine on EFS-induced contractile responses in the isolated urinary bladder detrusor strips of diabetic rats Berberine treatment potentiated EFS-induced contractile responses in the isolated urinary bladder detrusor strips of the normal and diabetic rats significantly, and the potentiation by 10μmol·L-1 berberine of the contractile responses to EFS at 32Hz in normal and diabetic rats was 42% and 49%, respectively.4 Effects of berberine on contractile responses to carbachol, KCl and ATP in the isolated urinary bladder detrusor strips of diabetic ratsCarbachol (0.01~30μmol·L-1), KCl (1~80mmol·L-1) and ATP (0.1~1000μmol·L-1) produced concentration-dependent contractile responses in the isolated urinary bladder detrusor strips of the normal and diabetic rats. There was no significant difference in the contractile responses to carbachol between normal and diabetic rats (P>0.05). The contractile responses to KCl in diabetic rats were significantly smaller than those to KCl in normal rats (P<0.01), but those to ATP in diabetic rats were significantly (P<0.05) increased in comparison with the contractile responses in normal rats. Phenylephrine (0.1~300μmol·L-1) did not produce any significant effects in the isolated urinary bladder detrusor strips of the normal and diabetic rats.Contractile responses to carbachol and KCl in the isolated urinary bladder detrusor strips of the normal and diabetic rats were not affected by berberine significantly (P>0.05). Berberine treatment, however, potentiated the contractile responses to ATP in the isolated urinary bladder detrusor strips of the normal and diabetic rats significantly. The potentiation by 10μmol·L-1 berberine of the contractile responses to 1mmol·L-1ATP in normal and diabetic rats was 89% and 97%, respectively.5 Effects of EFS, carbachol, ATP and KCl on the isolated urinary bladder detrusor strips of diuretic ratsThere were no significant differences in contractile responses of the isolated urinary bladder detrusor strips to EFS (1~32Hz), carbachol (0.01~30μmol·L-1), ATP (0.1~1000μmol·L-1) and KCl (1~80mmol·L-1) between diuretic rats and normal rats (P>0.05).Conclusion:In the early stage of diabetes onset, there were significant decreases in neurogenic contractile response to EFS and contractile response to KCl in the isolated urinary bladder detrusor strips of diabetic rats induced by streptozotocin in comparison with normal rats, and a noncholinergic component of the contractile response to EFS was obviously enlarged. Berberine significantly increased the neurogenic contractile response to EFS possibly via a postsynaptic potentiation of purinergic transmitter-regulated response in the isolated rat urinary bladder detrusor strips. Postsynaptic potentiation by berberine of purinergic contractile response was more evident in diabetic rats as compared with the normal rats.