| Full text | |
| Author(s): |
Lins, Bruna Bezerra
[1]
;
Casare, Fernando Augusto Malavazzi
[1]
;
Fontenele, Flavia Ferreira
[1]
;
Goncalves, Guilherme Lopes
[1]
;
Oliveira-Souza, Maria
[1]
Total Authors: 5
|
| Affiliation: | [1] Univ Sao Paulo, Lab Renal Physiol, Dept Physiol & Biophys, Inst Biomed Sci, Sao Paulo - Brazil
Total Affiliations: 1
|
| Document type: | Journal article |
| Source: | FRONTIERS IN PHYSIOLOGY; v. 12, APR 1 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
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) | |
| FAPESP's process: | 18/26528-5 - Adaptive mechanisms of renal function in a model of adriamycin-induced nephrotoxicity: participation of sirtuin 1 and claudin-1 |
| Grantee: | Guilherme Lopes Gonçalves |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 17/02020-0 - Mechanisms involved in the transition from post-ischemic acute kidney injury to chronic kidney disease: contribution of angiotensin II and albumin |
| Grantee: | Maria Oliveira de Souza |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 13/23087-4 - Molecular and functional study of membrane transporters |
| Grantee: | Gerhard Malnic |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 19/13584-7 - Mechanisms involved in the progression of renal diseases in experimental models of the adriamycin-induced nephrotoxicity or of the ischemia/reperfusion and Diabetes |
| Grantee: | Maria Oliveira de Souza |
| Support Opportunities: | Regular Research Grants |