Effects of Losartan on Renal Dopaminergic and Renin–Angiotensin System Alterations Induced by a High-Fat Diet in Sprague-Dawley Rats

The renal dopaminergic system (RDS) promotes natriuresis, diuresis, and exerts anti-inflammatory effects. High-fat diet (HFD) intake triggers the renin–angiotensin system (RAS). The aim of this study was to determine whether losartan (L) prevents RDS-RAS alteration and its impact on blood pressure and renal injury induced by HFD. Male Sprague–Dawley rats studied for 8 weeks were assigned to four groups: control (C; n = 4); HFD (n = 6): 50% w/w of bovine fat added to the standard diet; control + losartan (CL; n = 4): 30 mg/kg/day of L dissolved in drinking water; and HFD + losartan (HFDL; n = 6): HFD + CL. (Mean ± SD; p < 0.05). L prevented the following: HFD-induced increases in systolic blood pressure (SBP) and L-Dopa/dopamine urinary index (HFD vs. C, p < 0.01; HFDL vs. HFD, p < 0.01); lower expression of OCTN-1/2/3 (HFD vs. C, p < 0.01; HFDL vs. HFD, p < 0.05); overexpression of D1DR and Na+/K+-ATPase (HFD vs. C, p < 0.01; HFDL vs. HFD: D1DR p < 0.01; Na+/K+-ATPase p < 0.05), NF-κB1 and TGF-β1 (HFDL vs. HFD, p < 0.01). L mitigated proximal tubular alterations and interstitial fibrosis (HFDL vs. HFD, p < 0.01). Under chronic HFD intake, early L administration prevented renal dopaminergic system alterations and SBP elevation, and attenuated renal inflammation and interstitial fibrosis, reflecting its nephroprotective effects.