RT Journal Article T1 Bladder Dysfunction in an Obese Zucker Rat: The Role of TRPA1 Channels, Oxidative Stress, and Hydrogen Sulfide A1 Blaha, Igor A1 López-Oliva Muñoz, María Elvira A1 Martínez Sainz, María Del Pilar A1 Recio Visedo, María Paz A1 Agis Torres, Ángel A1 Martínez Gómez, Ana Cristina A1 Benedito Castellote, Sara A1 García Sacristán, Albino A1 Leite Fernandes, Vitor Samuel A1 Prieto Ocejo, Dolores A1 Hernández Rodríguez, Medardo Vicente AB Purpose: This study investigates whether functionality and/or expression changes of transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) channels, oxidative stress, and hydrogen sulfide (H2S) are involved in the bladder dysfunction from an insulin-resistant obese Zucker rat (OZR).Materials and methods: Detrusor smooth muscle (DSM) samples from the OZR and their respective controls, a lean Zucker rat (LZR), were processed for immunohistochemistry for studying the expression of TRPA1 and TRPV1 and the H2S synthase cystathionine beta-synthase (CBS) and cysthathionine-γ-lyase (CSE). Isometric force recordings to assess the effects of TRPA1 agonists and antagonists on DSM contractility and measurement of oxidative stress and H2S production were also performed.Results: Neuronal TRPA1 expression was increased in the OZR bladder. Electrical field stimulation- (EFS-) elicited contraction was reduced in the OZR bladder. In both LZR and OZR, TRPA1 activation failed to modify DSM basal tension but enhanced EFS contraction; this response is inhibited by the TRPA1 blockade. In the OZR bladder, reactive oxygen species, malondialdehyde, and protein carbonyl contents were increased and antioxidant enzyme activities (superoxide dismutase, catalase, GR, and GPx) were diminished. CSE expression and CSE-generated H2S production were also reduced in the OZR. Both TRPV1 and CBS expressions were not changed in the OZR.Conclusions: These results suggest that an increased expression and functionality of TRPA1, an augmented oxidative stress, and a downregulation of the CSE/H2S pathway are involved in the impairment of nerve-evoked DSM contraction from the OZR. PB Hindawi SN 1942-0900 YR 2019 FD 2019-08-20 LK https://hdl.handle.net/20.500.14352/98325 UL https://hdl.handle.net/20.500.14352/98325 LA eng NO Blaha I, López-Oliva ME, Martínez MP, Recio P, Agis-Torres Á, Martínez AC, Benedito S, García-Sacristán A, Prieto D, Fernandes VS, Hernández M. Bladder Dysfunction in an Obese Zucker Rat: The Role of TRPA1 Channels, Oxidative Stress, and Hydrogen Sulfide. Oxid Med Cell Longev. 2019 Aug 20;2019:5641645. doi: 10.1155/2019/5641645. PMID: 31531184; PMCID: PMC6721245 NO Universidad Complutense de Madrid NO Banco Santander DS Docta Complutense RD 23 jul 2024