gms | German Medical Science

Introduction: An enlargement of the urinary bladder occurs in all models of type 1 and many of type 2 diabetes (T2DM), but the underlying mechanisms are largely unknown. As angiotensin receptor antagonists are anti-hypertrophic in many tissues, we explored whether valsartan can attenuate bladder enlargement in a rat T2DM model.

Methods: A model of T2DM was induced by a combination of high-fat diet (HFD) + low-dose streptozotocin (STZ) in female Wistar rats (n = 14-21) in the absence and presence of treatment with valsartan (31 mg/kg/day starting 2 weeks after STZ and lasting for 8 weeks). Organ bath, histological and mRNA experiments were performed.

Results: HFD+STZ induced diabetes and markedly increased bladder weight (158 ± 50 mg vs. 178 ± 35 mg as compared to 89 ± 13 mg in control; primary outcome parameter). The enlargement was not accompanied by fibrosis (Masson-Goldner stain) or altered expression of collagen 1a or 3a or of TGF-β1 mRNA. Contractile responses to carbachol or KCl or relaxation responses to various β-adrenoceptor agonists (isoprenaline, fenoterol, CL 316,243) or to forskolin were not affected. Valsartan did not alter fibrosis or smooth muscle tone-associated parameters.

Conclusion: We conclude that valsartan did not mitigate bladder enlargement in a rat model of T2DM. Fibrosis and smooth muscle contractility were also not affected. These data further support that the pathophysiology of diabetes-associated bladder enlargement differs from that of non-diabetic causes of bladder hypertrophy.

Conflict of interest: MM is a consultant to Boehringer Ingelheim. The other authors report no conflict of interest.

This work was funded by DFG Mi 294-10/1 and TÜBITAK-SBAG 118S443. AA and ÖB have received fellowships from the Deutscher Akademischer Austauschdienst and from Erasmus+, respectively.