Long-Term Angiotensin II Infusion Induces Oxidative and Endoplasmic Reticulum Stress and Modulates Na+ Transporters Through the Nephron

Autor(es)

Lins, Bruna Bezerra ^[1] ; Casare, Fernando Augusto Malavazzi ^[1] ; Fontenele, Flavia Ferreira ^[1] ; Goncalves, Guilherme Lopes ^[1] ; Oliveira-Souza, Maria ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Lab Renal Physiol, Dept Physiol & Biophys, Inst Biomed Sci, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN PHYSIOLOGY; v. 12, APR 1 2021.
• Citações Web of Science: 0

Resumo

High plasma angiotensin II (Ang II) levels are related to many diseases, including hypertension, and chronic kidney diseases (CKDs). Here, we investigated the relationship among prolonged Ang II infusion/AT1 receptor (AT1R) activation, oxidative stress, and endoplasmic reticulum (ER) stress in kidney tissue. In addition, we explored the chronic effects of Ang II on tubular Na+ transport mechanisms. Male Wistar rats were subjected to sham surgery as a control or prolonged Ang II treatment (200 ng.kg(-1).min(-1), 42 days) with or without losartan (10 mg.kg(-1).day(-1)) for 14 days. Ang II/AT1R induced hypertension with a systolic blood pressure of 173.0 +/- 20 mmHg (mmHg, n = 9) compared with 108.0 +/- 7 mmHg (mmHg, n = 7) in sham animals. Under these conditions, gene and protein expression levels were evaluated. Prolonged Ang II administration/AT1R activation induced oxidative stress and ER stress with increased Nox2, Nox4, Cyba and Ncf1 mRNA expression, phosphorylated PERK and eIF2 alpha protein expression as well as Atf4 mRNA expression. Ang II/AT1R also raised Il1b, Nfkb1 and Acta2 mRNA expression, suggesting proinflammatory, and profibrotic effects. Regarding Na+ tubular handling, Ang II/AT1R enhanced cortical non-phosphorylated and phospho/S552/NHE3, NHE1, ENaC beta, NKCC2, and NCC protein expression. Our results also highlight the therapeutic potential of losartan, which goes beyond the antihypertensive effect, playing an important role in kidney tissue. This treatment reduced oxidative stress and ER stress signals and recovered relevant parameters of the maintenance of renal function, preventing the progression of Ang II-induced CKD. (AU)

• Processo FAPESP: 18/26528-5 - Mecanismos adaptativos da função renal em um modelo de nefrotoxicidade induzido por adriamicina: participação da sirtuína 1 e claudina-1
• Beneficiário: Guilherme Lopes Gonçalves
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/02020-0 - Mecanismos envolvidos na transição da injúria renal aguda pós-isquêmica para a doença renal crônica: contribuição da angiotensina II e da albumina
• Beneficiário: Maria Oliveira de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/23087-4 - Estudo molecular e funcional de transportadores de membrana
• Beneficiário: Gerhard Malnic
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/13584-7 - Mecanismos envolvidos na progressão de doenças renais em modelos experimentais de nefrotoxicidade induzida por adriamicina ou de isquemia/reperfusão e Diabetes
• Beneficiário: Maria Oliveira de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Regular