The effect of AT(2) and Mas receptors antagonists on renal hemodynamic and excretory disorders induced by ischemia/reperfusion in male and female rats

Abstract

Introduction: Renal ischemia-reperfusion (RIR) may disturb renin-angiotensin system components. In this study, the effects of Mas receptor (A779) and AT(2) receptor (PD123319) antagonists were examined in RIR rats. Methods: Total 60 male and female Wistar rats were assigned into 10 groups (n=6 in each group), including sham-operated group, RIR groups treated with the vehicle, A779, PD123319, or A779+PD123319. The rats were subjected to 30 minutes renal ischemia followed by 75 minutes reperfusion and the vehicle/antagonists were started to infuse 15 minutes after beginning of reperfusion for 60 min. Mean arterial pressure (MAP) and renal perfusion pressure responses to antagonists were assessed. Measurements for kidney function parameters also were performed. All the measurements were made at the end of 60 min vehicle/antagonist infusion. Results: MAP has altered significantly during RIR times (P=0.004), but no significant difference was observed between two genders. The RIR itself in injured rats (compared to sham operated rats) decreased urine flow (UF), creatinine clearance (Ccr), filtrate load of sodium (FNa) and sodium excretion rate (ENa) significantly in both genders (P<0.05). The antagonists infusion caused significant decrease in Ccr and FNa in male and female rats subjected to RIR when compared with vehicle (P<0.05), but the UF decreased significantly (P<0.05) only in PD123319 treated groups; however, there was no significant difference in ENa between the RIR groups in both genders. Conclusion: Our findings showed the importance role of Mas receptor and AT(2) receptor on renal function after kidney ischemia/reperfusion in RIR rat model.