ACE2-angiotensin-(1-7)-Mas axis in renal ischaemia/reperfusion injury in rats.
AngII (angiotensin II), ACE (angiotensin I-converting enzyme) and the AT1 receptor (AngII type 1 receptor) are associated with the inflammatory process and microvascular dysfunction of AKI (acute kidney injury) induced by renal I/R (ischaemia/reperfusion). However, Ang-(1-7) [angiotensin-(1-7)], ACE2 (angiotensin I-converting enzyme 2) and the Mas receptor also play a role in renal disease models. Therefore, in the present study, we have examined the renal profile of Ang-(1-7), ACE2 and the Mas receptor in renal I/R and compared them with that of AngII, ACE and the AT1 receptor. Male Wistar rats were submitted to left nephrectomy and ischaemia (45 min) followed by reperfusion (2 or 4 h) in the right kidney. At 4 h of reperfusion, renal AngII was increased (P<0.01) and renal Ang-(1-7) was decreased substantially (P<0.05), although plasma levels of both angiotensins were unchanged. In addition, renal I/R decreased the renal mRNA expression of renin (P<0.05), AT1 receptors (P<0.001) and ACE2 (P<0.05). At 2 and 4 h of reperfusion, renal ACE activity was reduced (P<0.05). On the other hand, renal expression of the Mas receptor was greatly increased at 4 h of reperfusion (P<0.01), which was confirmed by immunohistochemical and Western blot analysis. In conclusion, increased renal expression of the Mas receptor associated with changes in the RAS (renin-angiotensin system)-related peptidases support an important role for the ACE2-Ang-(1-7)-Mas axis in AKI.
Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
Kátia D
KD
da Silveira
Kênia S
KS
Pompermayer Bosco
Lúcio R L
LR
Diniz
Adriana K
AK
Carmona
Giovanni D
GD
Cassali
Oscar
O
Bruna-Romero
Lirlândia P
LP
de Sousa
Mauro M
MM
Teixeira
Robson A S
RA
Santos
Ana C
AC
Simões e Silva
Maria A
MA
Ribeiro Vieira
D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015427:Reperfusion Injury / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology; D014556:Urine
D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)