The renal antioxidative effect of losartan involves heat shock protein 70 in proximal tubule cells

Patricia G Vallés1,2, Victoria Bocanegra3, Valeria V Costantino3

  • 1Área de Fisiopatología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina. pvalles@fcm.uncu.edu.ar.

Insights

Losartan treatment enhances the protective heat shock protein 70 (HSP70) response in kidney cells of hypertensive rats, mitigating oxidative stress. This highlights HSP70

Area of Science:

  • Nephrology
  • Cardiovascular Research
  • Molecular Biology

Background:

  • Angiotensin II critically drives hypertension and kidney damage via AT1 receptors.
  • Local renin-angiotensin system (RAS) activity and intrarenal angiotensin II augment proximal tubular AT1 receptors.
  • NADPH oxidase activation, regulated by caveolin 1, is central to angiotensin II-induced kidney oxidative stress.

Purpose of the Study:

  • To investigate the role of heat shock protein 70 (HSP70) in regulating losartan-mediated antioxidative stress responses.
  • To examine the protective mechanisms of HSP70 in proximal tubule cells of spontaneously hypertensive rats (SHRs).

Main Methods:

  • Review of literature on renin-angiotensin system (RAS) activity in spontaneously hypertensive rats (SHRs).
  • Analysis of NADPH oxidase 4 (Nox4) expression and reactive oxygen species (ROS) production in kidney proximal tubules.
  • Examination of heat shock protein 70 (HSP70) synthesis and function in response to losartan treatment.

Main Results:

  • Angiotensin II upregulation induces oxidative stress in proximal tubules of SHRs, involving NADPH oxidase 4 (Nox4).
  • HSP70 acts as a molecular chaperone, critical for cellular recovery from stress and cytoprotection.
  • Losartan treatment's antioxidative effects are modulated by HSP70 in SHR proximal tubule cells.

Conclusions:

  • HSP70 plays a key role in mediating the antioxidative effects of losartan in the context of hypertension-induced kidney injury.
  • Targeting HSP70 may offer a therapeutic strategy to enhance renoprotection in hypertensive conditions.
  • Understanding HSP70 regulation is crucial for managing oxidative stress in kidney diseases associated with RAS activation.

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