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

Abstract

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.

Figure 1

Representative cystometrograms of saline-treated control (A) and diabetic (B) mice. Panels A1 and B1 show complete cystometrograms begun after emptying the bladder; although filling time was similar, the infusion rate for A was about 3 times higher than that for B. Panels A2 and B2 show the 20 seconds surrounding voiding, and panels A3 and B3 show the same data after bandpass filtering used to emphasize high-frequency oscillations attending phasic EUS contraction. DM = diabetes mellitus.

Figure 2

Cystometric variables in the four groups of mice (mean ± SEM). Abbreviations: veh = vehicle, Ang = AngII, DM = diabetes mellitus, conDur = contraction duration, and Pd = phasic duration. Significant differences are indicated in Table II.