RESUMEN
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.
Asunto(s)
Angiotensina II/metabolismo , Angiotensina I/metabolismo , Riñón/irrigación sanguínea , Fragmentos de Péptidos/metabolismo , Daño por Reperfusión/enzimología , Animales , Presión Sanguínea/fisiología , Riñón/metabolismo , Masculino , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/metabolismo , Ratas , Ratas Wistar , Receptores Acoplados a Proteínas G/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/fisiopatología , OrinaRESUMEN
Pharmacological strategies which limit neutrophil recruitment may also limit the damage induced by the reperfusion of an ischemic vascular territory. In the present study, we have investigated the effects of the BLT receptor antagonist, CP-105,696 ((+)-1-(3S,4R)-[3-(4-phenyl-benzyl)-4-hydroxy-chroman-7-yl]-cyclopentane carboxylic acid), on the local, remote and systemic inflammatory changes observed during severe intestinal ischemia (120 min) and reperfusion (120 min) injury. The post-ischemic treatment with CP-105,696 (3 mg/kg) virtually abolished the increase in vascular permeability, but not neutrophil accumulation, in the intestine and lungs. CP-105,696 partially inhibited the reperfusion-induced neutropenia, but failed to affect intestinal haemorrhage or lethality. CP-105,696 had no inhibitory effect on the local and systemic increases in the concentrations of tumour necrosis factor (TNF-alpha), interleukin-1 beta and interleukin-10, but markedly suppressed interleukin-6. Overall, our results show that activation of BLT receptor plays a minor role in the local, remote and systemic injuries following severe ischemia and reperfusion in rats.