Bladder Dysfunction in an Obese Zucker Rat: The Role of TRPA1 Channels, Oxidative Stress, and Hydrogen Sulfide

Blaha, Igor; López-Oliva Muñoz, María Elvira; Martínez Sainz, María Del Pilar; Recio Visedo, María Paz; Agis Torres, Ángel; Martínez Gómez, Ana Cristina; Benedito Castellote, Sara; García Sacristán, Albino; Leite Fernandes, Vitor Samuel; Prieto Ocejo, Dolores; Hernández Rodríguez, Medardo Vicente

Bladder Dysfunction in an Obese Zucker Rat: The Role of TRPA1 Channels, Oxidative Stress, and Hydrogen Sulfide

Download

OMCL2019-5641645.pdf (7.55 MB)

Official URL

https://doi.org/10.1155/2019/5641645

Publication date

2019

Publisher

Hindawi

Citations

Exportar

URI

https://hdl.handle.net/20.500.14352/98325

Citation

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

Abstract

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.