Sildenafil attenuates oxidative stress and endothelial dysfunction in lead-induced hypertension
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Data
2023-01-01
Autores
Caetano, Ediléia Souza Paula [UNESP]
Mattioli, Sarah Viana [UNESP]
da Silva, Maria Luiza Santos [UNESP]
Martins, Laisla Zanetoni [UNESP]
Almeida, Alaor Aparecido [UNESP]
da Rocha, Ananda Lini Vieira [UNESP]
Nunes, Priscila Rezeck [UNESP]
Grandini, Núbia Alves [UNESP]
Correa, Camila Renata [UNESP]
Zochio, Gabriela Palma [UNESP]
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Resumo
Lead (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.
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lead-induced hypertension, nitric oxide, oxidative stress, rats, sildenafil
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Basic and Clinical Pharmacology and Toxicology.