CARDIORENAL DYSFUNCTION IN MICE SUBMITTED TO AORTIC STENOSIS AND TREATED WITH SODIUM OXALATE

Abstract

Objective: The transverse aortic constriction (TAC) model mimics cardiac hypertrophy (CH) caused by hypertension. The model of kidney injury by consumption of soluble sodium oxalate (SO) in the feed also mimics lesions similar to hypertension. Our objective is to test the hypothesis that mice submitted to TAC and gavage with SO will represent an effective model of cardiorenal dysfunction. Design and method: Forty male C57BL mice were randomized into 4 groups: sham-operated animals that received gavage for 15 days with water or sodium oxalate (SO) and animals that received TAC and gavage also for 15 days with water or SO. In the fourth and eighth weeks, an echocardiogram was evaluated. Metabolic cage, direct hemodynamic recording, and histological analysis were performed in the eighth week. Data were analyzed using 1-2 way ANOVA followed by Bonferroni's posthoc, considering significant differences for p<0.05. Results: The TAC+SO group showed increased serum urea (SHAM:37.85±3 vs. TAC+SO:49.9±2.6mg/dL, p = 0.02) and, compared to the SHAM+SO group, a decrease in water consumption and water balance. The TAC+SO group had the highest systolic (SHAM:122.4±5.2 vs. TAC+SO:160±5.2mmHg, p<0.01), diastolic (SHAM:78.9±5.4 vs. TAC+SO:105±5mmHg, p<0.01) and mean pressure (SHAM:100.6±5 vs. TAC+SO:132±4.8mmHg, p<0.01) values. Compared to the SHAM+SO and the SHAM, TAC+SO showed increased double product (DP) (SHAM:64.6 ± 4.7 vs. SHAM+SO:62.7±3.3 vs. TAC+SO:96.6±5.2, p<0.01). The TAC group had the highest weight of corrected ventricles (SHAM:6.73 ± 0.1 vs.TAC:10±0.6mg/mm, p<0.01), and the TAC+SO group had the highest pulmonary congestion index. The SHAM+SO group showed increased autonomic modulation and HR variability, while the TAC+SO group showed an important reduction. TAC animals had the highest mean BP variability. The reflex tachycardia of the TAC, SHAM+SO and TAC+SO groups was very reduced, and only the TAC+SO group had a reduction in the alpha index. Conclusions: TAC surgery caused CH, reduction in reflex tachycardia, and changes in autonomic modulation. Gavage with SO for 15 days promoted primary renal injury, and separately it was able to increase autonomic modulation. TAC surgery associated with SO gavage caused greater cardiac and renal dysfunction.