**3. Results**

#### *3.1. Effects of Empagliflozin on Body Weight, Weights of Fat Depots, and Blood Pressure*

All three rat models gained weight during the study. However, there was decrease in body weight in uninephrectomized Hannover Sprague Dawley (HanSD) rats on high-salt diet (UNX + HS + empa), while renal artery stenosis (2K1C + empa) in Wistar rats had no effect on body weight. Empagliflozin (empa) decreased body weight in hypertensive fawn-hooded rats (FHH), while it had no effect on body weight in uninephrectomized rats on a high-salt diet or in rats with renal artery stenosis (Figure 2A,C,E and Tables 1–3). The relative food consumption was not different between untreated and empagliflozin-treated animals (14.3 ± 1.4 vs. 13.8 ± 1.2 in FHH rats; 15.2 ± 1.6 vs. 16.8 ± 2.1 in UNX+HS rats, and 12.8 ± 1.6 vs. 14.3 ± 1.4 in 2K1C rats, NS; g/100 g BW).

**Table 1.** Body and organ weights, as well as blood pressure and TBARS levels, in fawn-hooded hypertensive (FHH) rats treated with empagliflozin (empa).


\* denotes *<sup>p</sup>* < 0.05 vs. control group; **#** denotes *<sup>p</sup>* < 0.05 vs. untreated group; data are means ± SEM; and *<sup>n</sup>* = 7–10 for each group.

**Figure 2.** The effect of empagliflozin treatment on body weight (**A**,**C**,**E**) and systolic blood pressure (**B**,**D**,**F**) in fawn-hooded hypertensive (FHH) rats (**A**,**B**), uninephrectomized (UNX) Hannover Sprague Dawley (HanSD) rats on a high-salt (HS) diet (**C**,**D**), and Wistar rats subjected to renal artery stenosis (Goldblatt 2K1C hypertension) (**E**,**F**). \* *p* < 0.05 vs. control group, # *p* < 0.05 vs. untreated group. \* denotes *<sup>p</sup>* < 0.05; \*\* and ## denotes *<sup>p</sup>* < 0.01; \*\*\* denotes *<sup>p</sup>* < 0.001; data are means <sup>±</sup> SEM. Horizontal line in (**F**) depicts time points with significantly different BP levels.


**Table 2.** Body and organ weights as well as blood pressure and TBARS levels in uninephrectomized salt-loaded (UNX + HS) Hannover Sprague Dawley (HanSD) rats treated with empagliflozin (empa).

\* denotes *<sup>p</sup>* < 0.05 vs. control group; **#** denotes *<sup>p</sup>* < 0.05 vs. untreated group; data are means ± SEM; and *<sup>n</sup>* = 7–10 for each group.

**Table 3.** Body and organ weights, as well as blood pressure and TBARS levels, in Wistar rats subjected to renal artery stenosis (Goldblatt 2K1C hypertension) treated with empagliflozin (empa).


\* denotes *<sup>p</sup>* < 0.05 vs. control group; **#** denotes *<sup>p</sup>* < 0.05 vs. untreated group; data are means ± SEM; and *<sup>n</sup>* = 7–10 for each group.

There was no change in blood pressure (measured by tail-cuff plethysmography) in FHH rats during the experiment (Tables 1–3). Moreover, empagliflozin treatment did not modify blood pressure and relative heart weight in this strain. In contrast, blood pressure substantially increased (by about 60 mm Hg in HanSD-UNX+HS and 40 mm Hg in Wistar-2K1C) following surgical procedures in both experimentally induced CKD models (Figure 2B,D,F). This was followed by an increase in their relative heart weights. Empagliflozin had no effect on tail-cuff BP in either experimental group. This was also confirmed by a direct BP measurement at the end of the study. Visceral adiposity was decreased by empagliflozin treatment only in FHH rats. Relative kidney weight was increased in empagliflozin-treated FHH and in uninephrectomized salt-loaded rats, while it was unchanged in 2-kidney-1-clip rats.
