MYOCARDIAL FIBROSIS THERAPY SACUBITRIL/VALSARTAN OPTIONS IN ARTERIAL HYPERTENSION: AN EXPERIMENTAL STUDY

Highlights
The results obtained in this study demonstrate the feasibility of further investigation of the diagnostic ability of myocardial fibrosis markers in hypertension. This will further enable the exploration and implementation of more intensive treatment strategies to prevent hypertrophic and fibrotic myocardial remodeling, which can lead to complications in hypertension, as well as the study of the effects of other drugs on myocardial fibrosis.

Aim. To evaluate the effect of sacubitril/valsartan on myocardial fibrosis and galectin-3 and transforming growth factor-beta-1 levels in rats with arterial hypertension using morphological and biochemical methods.
Methods. Arterial hypertension was modeled by unilateral nephrectomy in 32 male Wistar rats. Animals were divided into four groups: control (sham-operated, n = 8), experimental (no treatment, n = 16), treatment-25 (model + sacubitril/valsartan 25 mg, n = 4), and treatment-50 (model + drug 50 mg, n = 4). Blood pressure was measured for 8 months. Cytokine levels were determined using enzyme-linked immunosorbent assay, and myocardial fibrosis was assessed using histological and morphometric methods.
Results. In the experimental group without drug administration, a significant increase in blood pressure, cardiomyocyte hypertrophy, an increase in TGF-β1 (13.1 ± 4.18 ng/mL), and fibrosis (median final score 4) were observed. Sacubitril/valsartan 50 mg reduced blood pressure (SBP 94.0 ± 1.6 mmHg) and TGF-β1 levels (8.44 ± 0.95 ng/mL) and prevented hypertrophy but had no effect on final fibrosis (median 4 points). However, fibrosis was absent in the interventricular and interatrial septa. Sacubitril/valsartan 25 mg had no effect on blood pressure or final fibrosis (median 6 points). Galectin-3 levels did not differ between groups. ROC analysis showed low diagnostic significance of the studied cytokines (AUC < 0.73).
Conclusion. Sacubitril/valsartan 50 mg exerted a significant hypotensive and antihypertrophic effect, partially preventing fibrosis in the interatrial and interventricular septa, but did not prevent the development of overall myocardial fibrosis.

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