The effects of Ins2(Akita) diabetes and chronic angiotensin II infusion on cystometric properties in mice

• Published in: Neurourology and urodynamics Vol. 34; no. 1; pp. 72 - 78
• Main Authors: Dolber, Paul C., Jin, Huixia, Nassar, Rashid, Coffman, Thomas M., Gurley, Susan B., Fraser, Matthew O.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-01-2015; Wiley Subscription Services, Inc
• Subjects: Angiotensin II - administration & dosage; Animals; bladder; cystometry; detrusor; Diabetes Mellitus, Experimental - physiopathology; Diabetes Mellitus, Type 1 - physiopathology; diabetic cystopathy; diabetic uropathy; lower urinary tract; Male; Mice; renin-angiotensin system; Urinary Bladder - drug effects; Urinary Bladder - physiopathology; Urinary Bladder Diseases - physiopathology; Urination - drug effects; Urination - physiology; voiding efficiency
• ISSN: 0733-2467; 1520-6777
• DOI: 10.1002/nau.22511

Aims
Diabetes is associated with both dysfunction of the lower urinary tract (LUT) and overactivity of the renin‐angiotensin system (RAS). Although it is well known that the RAS affects normal LUT function, very little is known about RAS effects on the diabetic LUT. Accordingly, we investigated the effects of chronic angiotensin II (AngII) treatment on the LUT in a model of type 1 diabetes.
Methods
Ins2(Akita) diabetic mice (20 weeks old) and their age‐matched background controls underwent conscious cystometric evaluation after 4 weeks of chronic AngII treatment (700 ng/kg/min by osmotic pump) or vehicle (saline).
Results
Diabetic mice had compensated LUT function with bladder hypertrophy. Specifically, micturition volume, residual volume, and bladder capacity were all increased, while voiding efficiency and pressure generation were unchanged as bladder mass, contraction duration, and phasic urethral function were increased. AngII significantly increased voiding efficiency and peak voiding pressure and decreased phasic frequency irrespective of diabetic state and, in diabetic but not normoglycemic control mice, significantly decreased residual volume and increased contraction duration and nonphasic contraction duration.
Conclusions
The Ins2(Akita) diabetic mice had compensated LUT function at 20 weeks of age. Even under these conditions, AngII had beneficial effects on LUT function, resulting in increased voiding efficiency. Future studies should therefore be conducted to determine whether AngII can rescue the decompensated LUT function occurring in end‐stage diabetic uropathy. Neurourol. Urodynam. 34:72–78, 2015. © 2013 Wiley Periodicals, Inc.