NLRP3 Inflammasomes Contribute to the Impaired Bladder Contraction in Male Diabetic Mice

Abstract

BackgroundNLRP3 inflammasomes activation has been demonstrated in both type 1 and type 2 diabetes mellitus and it has been correlated with dysfunctional organs. Although it has been shown that activation of NLRP3 inflammasomes contributes to bladder dysfunction in models of cystitis and bladder outlet obstruction, it is still unknown whether inflammasomes contribute to the development of diabetic bladder dysfunction.AimWe aimed to evaluate the contribution of NLRP3 inflammasomes in the late phase of diabetic bladder dysfunction which is known by hypo responsiveness of the detrusor smooth muscle.MethodsStrips of bladder were excised from male and female wild type (WT) and dbdb−/− mice at 14 – 16 week old and were mounted in a muscle strip myograph system. Contraction of the bladder was evaluated by a single concentration of KCl (120 mM), concentration‐response curves to carbachol (1 nM – 30 μM) and frequency‐response curves to electrical field stimulation (EFS: 1–16 Hz). Carbachol and EFS were repeated in the presence of the NLRP3 inhibitor MCC950 (1 μM).ResultsMale bladder strips presented higher magnitude of contraction than female bladder strips for all contractile agents tested. KCl‐induced contraction was similar in both strains (Female WT: 42 ± 7 mN; dbdb−/−: 40 ± 4 mN; Male WT: 54 ± 6.5 mN; dbdb−/−: 51 ± 17 mN). In males, the potency of carbachol was lower in the bladder of dbdb−/− mice (pEC50: 5.53 ± 0.09) compared to WT (pEC50: 6.11 ± 0.07) and it was not restored in the presence of MCC950 (pEC50: 5.66 ± 0.08). Similarly, the contraction induced by EFS was significantly reduced for all frequencies in the bladder of male dbdb−/− mice (at 16 Hz: 51 ± 10 mN) compared to WT (at 16 Hz: 77 ± 3 mN). However, it was restored in the presence of MCC950 (at 16 Hz: 71 ± 11 mN). In female mice, there was no difference in the contraction of the bladder of dbdb−/− mice when compared to WT and addition of MCC950 did not altered the responses neither in WT nor in dbdb−/−.ConclusionIn conclusion, our data suggest that NLRP3 inflammasomes contribute to the development of hypoactive detrusor response in the late phase of diabetic bladder dysfunction in males.Support or Funding InformationNational Institute of Health (NIH; HL‐134604) São Paulo Research Foundation (FAPESP; 2016/20592‐8)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.