ACE2-angiotensin-(1-7)-Mas axis in renal ischaemia/reperfusion injury in rats

AngII (angiotensin II), ACE (angiotensin I-converting enzyme) and the AT(1) receptor (AngII type I 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 AT(1) 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), AT(1) 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.