#1682 Myocardial remodeling in Wistar rats with renal dysfunction treated with a high-salt ration
Authors: Khasun Mokhamad , Ivanova Galina , Parastaeva Marina , Bogdanova Evdokia , Rumyantsev Aleksander , Kucher Anatoly , Beresneva Olga 
Published: May 2024

Abstract

Background and Aims
High food intake of NaCl is the traditional factor of increase in blood pressure (BP) and cardiovascular risks also hurts kidneys. The purpose of the paper is to evaluate the morphological changes in the myocardium of normotensive Wistar rats with an early stage of renal dysfunction treated with a diet with increased concentration of salt for a long time.

Method
30 Wistar rats (age 2.5-3 months) were studied and divided into three groups of 10 each. In the first, control, sham-operated (SO) rats, receiving standard diet (0.34% NaCl), in the second, rats subjected to resection of ¾ of the kidney parenchyma, receiving a standard diet (NE group), in the third, rats subjected to ¾ NE and those receiving a high-sodium diet (4% NaCl, high-salt diet, HSD). The feeds differed only in the %NaCl content. The ¾ NE model was created in two stages with an interval of 7 days. 20 mg/kg Zoletil 100 and 0.05 ml of Xylazine were used as anesthesia. At the first stage, the poles of the left kidney (1/2 part of the kidney) were removed, at the second stage, the right kidney was completely removed. The duration of the experiment was 4 months. At the end of the experiment, systolic BP at the tail was measured in awake rats using the cuff method (ELEMA electromanometer, Sweden). After removal from the experiment, blood was collected from the rats for biochemical analysis, and the LVMI was calculated as the ratio of LV mass to the body weight of the animal (mg/g). Myocardial fragments were placed in formalin, and sections 1.5–2 µm thick were prepared from paraffin blocks. The preparations were stained with Hematoxylin and Eosin and Masson's trichrome and used for histological analysis. The statistical significance of intergroup differences was determined using the Mann–Whitney test and Student's t test.

Results
During the observation period, BP in the SO group of animals did not change: initially - 120 [120;125] mm Hg, after 4 months - 120 [120;125] mmHg, p = 0.527. In the group with NE on a standard diet, an increase in BP was noted - from 120 [120; 125] mmHg up to 135.0 [132.5;137.5] mmHg, p = 0.011. In the group with NE + HSD, the increase in BP levels was more pronounced - up to 140[140;148] mmHg, (p = 0.001, relative to the SO group). The serum urea level in the SO group was 4.7 [4.5;5.4] mmol/l, creatinine −32.5 [29.0;36.0] µmol/l, in the NE group - 10.0 [9.1;10.9] mmol/l, (p = 0.0001, relative to the SO group) and 69.0[64.0;74.0] µmol/l, (p = 0.0001), in the NE+ HSD group – 10.7 [9.8;11.0] mmol/l, (p = 0.0001) and 64.5[46.3;69.5] µmol/l, (p = 0.001), respectively. Thus, the groups of rats with early-stage kidney dysfunction, although they had higher levels of urea and creatinine in the blood serum relative to the SO group, did not differ significantly from each other in these indicators. LVMI increased in rats with NE on a standard diet (LR −2.07±0.05 mg/g, NE −2.14 ± 0.06 mg/g, p = 0.1591). Consumption of a high-salt diet aggravated the growth of myocardial mass in rats with NE (NE + HSD - 2.41 ± 0.14 mg/g, p = 0.0084 and p = 0.0372, respectively). At the histological level, the increase in LV myocardial mass in rats with NE was characterized by hypertrophy of cardiomyocytes and the formation of interstitial fibrosis. The changes were more pronounced in the group with NE + HSD. The diameter of cardiomyocytes in rats of the SO group was 12.9 ± 0.4 µm, in animals with NE on standard diet - 14.5 ± 0.6 µm, in rats with NE + HSD - 15.5 ± 1.6 µm (p&lt;0 .01 and p &lt; 0.02, relative to the SO group). The area of interstitial fibrosis also increased in rats with NE (10.5 ± 2.6%, in the SO group - 0.6 ± 0.2%, p = 0.0000) and was slightly higher in the NE + HSD group (13.6 ± 2.8%, p = 0.0000, relative to the SO group). In rats with NE, both on a standard diet and with HSD, at this stage of the formation of kidney pathology, the thickness of the nutrimyocardial arteries did not differ significantly from the SO indicator rats.

Conclusion
Long-term salt intake with increased salt addition in Wistar rats in the initial stages of renal dysfunction does not affect the level of urea and creatinine in the blood serum, but promotes an increase in BP and myocardial remodeling, constantly progressing in the progression of cardiomyocyte hypertrophy and interstitial fibrosis.