Sildenafil attenuates oxidative stress and endothelial dysfunction in lead-induced hypertension

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dc.contributor.authorCaetano, Ediléia Souza Paula [UNESP]
dc.contributor.authorMattioli, Sarah Viana [UNESP]
dc.contributor.authorda Silva, Maria Luiza Santos [UNESP]
dc.contributor.authorMartins, Laisla Zanetoni [UNESP]
dc.contributor.authorAlmeida, Alaor Aparecido [UNESP]
dc.contributor.authorda Rocha, Ananda Lini Vieira [UNESP]
dc.contributor.authorNunes, Priscila Rezeck [UNESP]
dc.contributor.authorGrandini, Núbia Alves [UNESP]
dc.contributor.authorCorrea, Camila Renata [UNESP]
dc.contributor.authorZochio, Gabriela Palma [UNESP]
dc.contributor.authorDias-Junior, Carlos Alan [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.date.accessioned2023-07-29T13:58:33Z
dc.date.available2023-07-29T13:58:33Z
dc.date.issued2023-01-01
dc.description.abstractLead (Pb) reduces NO bioavailability, impairs the antioxidant system, and increases the generation of reactive oxygen species (ROS). Pb-induced oxidative stress may be responsible for the associated endothelial dysfunction. Sildenafil has shown nitric oxide (NO)-independent action, including antioxidant effects. Therefore, we examined the effects of sildenafil on oxidative stress, reductions of NO and endothelial dysfunction in Pb-induced hypertension. Wistar rats were distributed into three groups: Pb, Pb + sildenafil and Sham. Blood pressure and endothelium-dependent vascular function were recorded. We also examined biochemical determinants of lipid peroxidation and antioxidant function. ROS levels, NO metabolites and NO levels in human umbilical vein endothelial cells (HUVECs) were also evaluated. Sildenafil prevents impairment of endothelium-dependent NO-mediated vasodilation and attenuates Pb-induced hypertension, reduces ROS formation, enhances superoxide dismutase (SOD) activity and antioxidant capacity in plasma and increases NO metabolites in plasma and HUVECs culture supernatants, while no changes were found on measurement of NO released from HUVECs incubated with plasma of the Pb and Pb + sildenafil groups compared with the sham group. In conclusion, sildenafil protects against ROS-mediated inactivation of NO, thus preventing endothelial dysfunction and attenuating Pb-induced hypertension, possibly through antioxidant effects.en
dc.description.affiliationDepartment of Pharmacology Biosciences Institute of Botucatu Sao Paulo State University (UNESP)
dc.description.affiliationCenter of Toxicological Assistance (CEATOX) Biosciences institute of Botucatu Sao Paulo State University (UNESP)
dc.description.affiliationMedical School Sao Paulo State University (UNESP)
dc.description.affiliationUnespDepartment of Pharmacology Biosciences Institute of Botucatu Sao Paulo State University (UNESP)
dc.description.affiliationUnespCenter of Toxicological Assistance (CEATOX) Biosciences institute of Botucatu Sao Paulo State University (UNESP)
dc.description.affiliationUnespMedical School Sao Paulo State University (UNESP)
dc.identifierhttp://dx.doi.org/10.1111/bcpt.13904
dc.identifier.citationBasic and Clinical Pharmacology and Toxicology.
dc.identifier.doi10.1111/bcpt.13904
dc.identifier.issn1742-7843
dc.identifier.issn1742-7835
dc.identifier.scopus2-s2.0-85161450477
dc.identifier.urihttp://hdl.handle.net/11449/248960
dc.language.isoeng
dc.relation.ispartofBasic and Clinical Pharmacology and Toxicology
dc.sourceScopus
dc.subjectlead-induced hypertension
dc.subjectnitric oxide
dc.subjectoxidative stress
dc.subjectrats
dc.subjectsildenafil
dc.titleSildenafil attenuates oxidative stress and endothelial dysfunction in lead-induced hypertensionen
dc.typeArtigo
unesp.author.orcid0000-0002-0348-6144[11]

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Artigos - Farmacologia - IBB
Botucatu - CEATOX - Centro de Assistência Toxicológica