title: Alternative pathways for angiotensin II production as an important determinant of kidney damage in endotoxemia.
abstract: Sepsis is an uncontrolled systemic inflammatory response against an infection and a major public health issue worldwide. This condition affects several organs, and, when caused by Gram-negative bacteria, kidneys are particularly damaged. Due to the importance of renin-angiotensin system (RAS) in regulating renal function, in the present study, we aimed to investigate the effects of endotoxemia over the renal RAS. Wistar rats were injected with Escherichia coli lipopolysaccharide (LPS) (4 mg/kg), mimicking the endotoxemia induced by Gram-negative bacteria. Three days after treatment, body mass, blood pressure, and plasma nitric oxide (NO) were reduced, indicating that endotoxemia triggered cardiovascular and metabolic consequences and that hypotension was maintained by NO-independent mechanisms. Regarding the effects in renal tissue, inducible NO synthase (iNOS) was diminished, but no changes in the renal level of NO were detected. RAS was also highly affected by endotoxemia, since renin, angiotensin-converting enzyme (ACE), and ACE2 activities were altered in renal tissue. Although these enzymes were modulated, only angiotensin (ANG) II was augmented in kidneys; ANG I and ANG 1-7 levels were not influenced by LPS. Cathepsin G and chymase activities were increased in the endotoxemia group, suggesting alternative pathways for ANG II formation. Taken together, our data suggest the activation of noncanonical pathways for ANG II production and the presence of renal vasoconstriction and tissue damage in our animal model. In summary, the systemic administration of LPS affects renal RAS, what may contribute for several deleterious effects of endotoxemia over kidneys.
authors.affiliation: Medicine Department, Nephrology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil; and.
authors.forename: Rodolfo Mattar
authors.initials: RM
authors.lastname: Rosa
authors.affiliation: Medicine Department, Nephrology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil; and.
authors.forename: Juliana Almada
authors.initials: JA
authors.lastname: Colucci
authors.affiliation: Medicine Department, Nephrology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil; and.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Yokota
authors.affiliation: Medicine Department, Nephrology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil; and.
authors.forename: Roseli Peres
authors.initials: RP
authors.lastname: Moreira
authors.affiliation: Medicine Department, Nephrology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil; and.
authors.forename: Danielle Sanches
authors.initials: DS
authors.lastname: Aragão
authors.affiliation: Medicine Department, Nephrology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil; and.
authors.forename: Amanda Aparecida
authors.initials: AA
authors.lastname: Ribeiro
authors.affiliation: Medicine Department, Nephrology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil; and.
authors.forename: Danielle Yuri
authors.initials: DY
authors.lastname: Arita
authors.affiliation: Medicine Department, Nephrology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil; and.
authors.forename: Ingrid Kazue Mizuno
authors.initials: IK
authors.lastname: Watanabe
authors.affiliation: Medicine Department, Nephrology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil; and.
authors.forename: Zaira
authors.initials: Z
authors.lastname: Palomino
authors.affiliation: Science and Technology Department, Instituto de Ciência e Tecnologia, Universidade Federal de São Paulo, São José dos Campos, Brazil.
authors.forename: Tatiana Sousa
authors.initials: TS
authors.lastname: Cunha
authors.affiliation: Medicine Department, Nephrology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil; and casarini.elena@unifesp.br.
authors.forename: Dulce Elena
authors.initials: DE
authors.lastname: Casarini
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology
chemical_list: D008070:Lipopolysaccharides; D000804:Angiotensin II; D009569:Nitric Oxide; D000803:Angiotensin I; D052247:Nitric Oxide Synthase Type II; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D012083:Renin
keywords: acute kidney injury; endotoxemia; renin-angiotensin system