Effect of diabetes on cooling-induced detrusor muscle contraction: mediation via Rho-kinase activation.
OBJECTIVE
To investigate the possible involvement of Rho-kinase in cooling-induced contraction of the detrusor muscle. The etiology of diabetic cystopathy is not clear. It may be due to various changes in bladder innervation and/or detrusor muscle dysfunction. Because cooling of urinary bladder smooth muscle normally is a potent stimulus to micturition due to increase in muscle tone, we studied the effects of cooling on normal and diabetic bladder specimens.


METHODS
Urinary detrusor muscle strips isolated from rats were suspended in organ baths containing Krebs solution for isometric tension recording. Tissue responses to stepwise cooling were examined from normal and 12-week streptozocin-induced diabetic rats. We examined the effects of calcium-free, ethylene glycol bis (beta-aminoethylether)-N,N,N,N,-tetraacetic acid (1 mm)-containing Krebs solution, and the Rho-kinase inhibitor Y-27632 on the cooling responses.


RESULTS
Stepwise cooling from 37 degrees C to 5 degrees C induced a rapid and reproducible increase in basal tone, proportional to cooling temperature. This response was more pronounced in diabetic specimens. Cooling-induced contractions were significantly inhibited in calcium-free solutions in both control and diabetic bladders. Our investigation showed that the influx of extracellular calcium is important in inducing the cooling response. The Rho-kinase inhibitor Y-27632 (1 microm) inhibited cooling (20 degrees C)-induced contraction. It reduced the response by 52.1% +/- 10.0% in control and by 70.0% +/- 12.0% in diabetic rats.


CONCLUSIONS
Cooling-induced contractions in control and diabetic detrusor muscle preparations are highly calcium dependant. It also involves activation of Rho-kinase, which might be upregulated in the diabetic detrusor muscle. These results may help in the management of diabetes-induced incontinence due to involuntary detrusor muscle activity.
Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Jackson Memorial Medical Center, Florida, USA.
Hishaam N
HN
Ismael
Seham
S
Mustafa
Olav
O
Thulesius
D000818:Animals; D003080:Cold Temperature; D003920:Diabetes Mellitus / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000503:physiopathology*; D054460:rho-Associated Kinases / Q000502:physiology*
D054460:rho-Associated Kinases