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ORIGINAL RESEARCH article

Front. Physiol.
Sec. Integrative Physiology
Volume 15 - 2024 | doi: 10.3389/fphys.2024.1369120
This article is part of the Research Topic Novel Mechanisms Involved in Urinary Bladder Control: Advances in Neural, Humoral and Local Factors Underlying Function and Disease, Volume III View all 7 articles

Impact of Intravascular Hemolysis on Functional and Molecular Alterations in the Urinary Bladder: Implications for Overactive Bladder in Sickle Cell Disease

Provisionally accepted
Tammyris H. Silveira Tammyris H. Silveira 1DALILA A. PEREIRA DALILA A. PEREIRA 1Danillo A. Pereira Danillo A. Pereira 1Fabiano B. Calmasini Fabiano B. Calmasini 2Arthur Burnett Arthur Burnett 3Fernando F. Costa Fernando F. Costa 4FABIO H. SILVA FABIO H. SILVA 5*
  • 1 São Francisco University Medical School, Bragança Paulista, Brazil
  • 2 Departamento de Farmacologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil
  • 3 The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • 4 Hematology and Hemotherapy Center, University of Campinas, Campinas, São Paulo, Brazil
  • 5 Sao Francisco University, Braganca Paulista, Brazil

The final, formatted version of the article will be published soon.

    Patients with sickle cell disease (SCD) display overactive bladder (OAB). Intravascular hemolysis in SCD is associated with various severe SCD complications. However, no experimental studies evaluated the effect of intravascular hemolysis on bladder function. This study aimed to assess the effects of intravascular hemolysis on the micturition process and the contractile mechanisms of the detrusor smooth muscle (DSM) in a mouse model with phenylhydrazine (PHZ)-induced hemolysis, as well as the role of intravascular hemolysis in dysfunction of nitric oxide (NO) signaling and in increasing the stress oxidative and in the bladder. Mice underwent void spot assay, and DSM contractions were evaluated in organ baths. PHZ group exhibited increased urinary frequency and increased void volumes. DSM contractile responses to carbachol, KCl, αβ-methylene-ATP, and EFS were increased in the PHZ group. Protein expression of phosphorylated endothelial NO synthase (eNOS) (Ser-1177), phosphorylated neuronal NO synthase (nNOS) (Ser-1417), and phosphorylated vasodilator-stimulated phosphoprotein (VASP) (Ser-239) decreased in the bladder of PHZ group. Protein expression of oxidative stress markers, NOX-2, 3-NT, and 4-HNE, increased in the bladder of the PHZ group. Our study shows that intravascular hemolysis promotes voiding dysfunction correlated with to alterations in the NO signaling pathway in the bladder, as evidenced by reduced levels of p-eNOS (Ser-1177), nNOS (Ser-1417), and p-VASP (Ser-239). The study also showed that intravascular hemolysis increases oxidative stress in the bladder. Our study indicates that intravascular hemolysis promotes OAB phenotype similar to those observed in patients and mice with SCD.

    Keywords: cGMP, Nitric Oxide, Oxidative Stress, NADPH Oxidase, Urinary dysfunction

    Received: 11 Jan 2024; Accepted: 20 May 2024.

    Copyright: © 2024 Silveira, PEREIRA, Pereira, Calmasini, Burnett, Costa and SILVA. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: FABIO H. SILVA, Sao Francisco University, Braganca Paulista, Brazil

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