Inhibitors of the Renin‐Angiotensin System (RAS) Completely Prevents Cardiac Hypertrophy (CH) Induced by Ischemic Renal Injury (IRI) via Angiotensin II (AngII)/Toll‐Like Receptors (TLR) Cross‐Talk

Abstract

ObjectivesThe cardio‐renal syndrome comprises a set of pathophysiological kidney‐heart interactions. Renal injury promotes release of inflammatory cytokines (CTK), which may act through cardiac TLR and lead to CH, as well as AngII. This study aims to investigate a possible interaction between TLR and RAS in CH model induced by IRI.MethodsC57BL/6 male mice (n=84) treated with Losartan (Los‐10 mg/kg) or Enalapril (Ena‐40 mg/kg) were subjected to surgical occlusion of left renal pedicle and kept under observation for 20d. IRI, CH and systolic blood pressure (SBP) were assessed by morphologic, molecular and functional parameters, as well as tail‐cuff plethysmography and electrocardiography (ECG) before and after surgery. Serum/cardiac RAS components, TLR2/TLR4 and inflammatory CTK were evaluated by Real‐Time PCR, protein expression and ELISA.ResultsThe successfully‐performed IRI induced an enhancement of serum IL‐6, TNF‐a and IFN‐y (p<0.001) and did not promote SBP alteration. CH was observed after 12d of reperfusion, when cardiac AT1, ACE2, TLR2/TLR4 levels were increased (p<0.001). Los/Ena prevented CH (p<0.001) without changing SBP and modulated serum AngII and CTK levels (p<0.05). Also, ECG showed an improvement in cardiac function.ConclusionThe presented data shows that RAS inhibition is able to completely prevent CH via regulation of cardiac TLR and serum AngII/CTK levels, suggesting the existence of a key cross‐talk between TLR and RAS in CH induced by IRI. Financial Support: FAPESP; CNPq.