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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

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

  • Silvana M. Cantú1,2
  • Hyun J. Lee1,2
  • Christian Höcht3
  • Adriana S. Donoso1,2
  • Rodolfo Valtuille4
  • Ana M. Puyó1,2
  • Marcelo R. Choi1,5
5 affiliations
  1. 1Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Ciencias Biológicas, Cátedra de Anatomía e Histología, Buenos Aires 1113, Argentina
  2. 2Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Laboratorio de Síndrome Metabólico Experimental, Buenos Aires 1113, Argentina
  3. 3Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Farmacología, Cátedra de Farmacología, Buenos Aires 1113, Argentina
  4. 4Pontificia Universidad Católica Argentina, Especialización en Nefrología, Facultad de Ciencias Médicas, Buenos Aires 1113, Argentina
  5. 5Universidad de Buenos Aires/Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional (IATIMET), Buenos Aires 1113, Argentina
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{cantu2026effects,
  title = {{Effects of Losartan on Renal Dopaminergic and Renin–Angiotensin System Alterations Induced by a High-Fat Diet in Sprague-Dawley Rats}},
  author = {Silvana M. Cantú and Hyun J. Lee and Christian Höcht and Adriana S. Donoso and Rodolfo Valtuille and Ana M. Puyó and Marcelo R. Choi},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27209098},
  url = {https://www.mdpi.com/1422-0067/27/20/9098},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Effects of Losartan on Renal Dopaminergic and Renin–Angiotensin System Alterations Induced by a High-Fat Diet in Sprague-Dawley Rats
AU  - Silvana M. Cantú
AU  - Hyun J. Lee
AU  - Christian Höcht
AU  - Adriana S. Donoso
AU  - Rodolfo Valtuille
AU  - Ana M. Puyó
AU  - Marcelo R. Choi
PY  - 2026
DA  - 2026/10/14
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27209098
UR  - https://www.mdpi.com/1422-0067/27/20/9098
AB  - 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.
SN  - 1422-0067
ER  -