Effect of Sacubitril/Valsartan on Hemodynamic Parameters, Biomarkers of Inflammation and Cardiac Remodeling in Rats with DOCA-Salt-Induced Hypertension

The aim of the study was to assess the influence of Sacubitril/Valsartan (S/V) on hemodynamic indices and heart remodeling events in rats with DOCA-salt arterial hypertension (AH). Experiments were performed on Wistar rats. Animals were randomly divided into the four groups: (I) Control (C) group, (II) DOCA-salt group, (III) S/V + DOCA -salt as drinking water, and (IV) S/V after development of DOCA-salt hypertension. Heart beat (HB)/min and systolic and diastolic blood pressure (SBP, DBP, mmHg) were obtained by tail-cuff method in the morning hours. The level of ET-1, IL-1, TNF-alpha, and NF-kB transcription factor were measured in the blood plasma of rats by ELISA kits method. Morphometric and histomorphological changes in heart and aorta were analyzed in the tissue sections using electronical microscope. In the second group of animals, the mean values of SBP – 153,6 ± 5,4 mmHg, DBP – 67,9 ± 2,8 mmHg, and HB – 394 ± 12/min were significantly increased in comparison with C group of animals (123,0 ± 5,2 mmHg (p 0,001), 55,6 ± 3,0 mmHg (p 0,05), and 361 ± 24/min (p 0,001), respectively). Such alterations in cardiovascular parameters correlated with marked increase in DOCA-salt group blood plasma levels of ET-1, IL-1, TNF-alpha, and NF-kB vs. C animals. S/V treatment significantly reduced SBP, DBP, and HB (-30,2 ± 4 mmHg, (p 0,001), -11,4 ± 2,2 mmHg (p 0,05), and -33 ± 12/min, p 0,002, respectively) in hypertensive rats (HR) associated with marked decrease in blood levels of ET-1 (56,9%, p 0,01), IL-1 (67,3%, p 0,001), TNF-alpha (75,1%, p 0,001), and NF-kB (59,2%, p 0,001), with significant improvement of morphological changes of the heart in this group of animals. It is suggested that S/V in hypertensive state exerts a positive effect on hemodynamic parameters, providing reverse action on heart remodeling and can be considered as a valuable drug for the AH treatment and prevention of structural changes in target organs.