Renoprotective Effects of AVE0991, a Nonpeptide Mas Receptor Agonist, in Experimental Acute Renal Injury.
Renal ischemia and reperfusion (I/R) is the major cause of acute kidney injury in hospitalized patients. Mechanisms underlying reperfusion-associated injury include recruitment and activation of leukocytes and release of inflammatory mediators. In this study, we investigated the renal effects of acute administration of AVE0991, an agonist of Mas, the angiotensin-(1-7) receptor, the angiotensin-(1-7) receptor, in a murine model of renal I/R. Male C57BL/6 wild-type or Mas(-/-) mice were subjected to 30 min of bilateral ischemia and 24 h of reperfusion. Administration of AVE0991 promoted renoprotective effects, as seen by improvement of function, decreased tissue injury, prevention of local and remote leucocyte infiltration, and release of the chemokine, CXCL1. I/R injury was similar in WT and Mas(-/-) mice, suggesting that endogenous activation of this receptor does not control renal damage under baseline conditions. In conclusion, pharmacological interventions using Mas receptor agonists may represent a therapeutic opportunity for the treatment of renal I/R injury.
Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, UFMG, 31270-901 Belo Horizonte, MG, Brazil.
Lívia Corrêa
LC
Barroso
Kátia Daniela
KD
Silveira
Cristiano Xavier
CX
Lima
Valdinéria
V
Borges
Michael
M
Bader
Milene
M
Rachid
Robson Augusto Souza
RA
Santos
Danielle Gloria
DG
Souza
Ana Cristina
AC
Simões E Silva
Mauro Martins
MM
Teixeira