Related Experiment Video
Updated: Dec 20, 2025

Author Spotlight: Exploring Huotan Jiedu Tongluo Decoction as an Antihypertensive Drug
Published on: May 17, 2024
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.
Abstract:
Angiotensin II exerts a cardinal role in the pathogenesis of hypertension and renal injury via action of angiotensin II type 1 (AT1) receptors. Local renin-angiotensin system (RAS) activity is essential for the mechanisms mediating pathophysiological functions. Proximal tubular angiotensinogen and tubular AT1 receptors are augmented by intrarenal angiotensin II. Caveolin 1 plays an important role as a regulatory molecule for the compartmentalization of redox signaling events through angiotensin II-induced NADPH oxidase activation in the kidney. A role for the renin-angiotensin system in the development and/or maintenance of hypertension has been demonstrated in spontaneously hypertensive rats (SHRs). Many effects of angiotensin II are dependent on the AT1 stimulation of reactive oxygen species (ROS) production by NADPH oxidase. Angiotensin II upregulation stimulates oxidative stress in proximal tubules from SHR. The NADPH oxidase 4 (Nox4) is abundantly expressed in kidney proximal tubule cells. Induction of the stress response includes synthesis of heat shock protein 70, a molecular chaperone that has a critical role in the recovery of cells from stress and in cytoprotection, guarding cells from subsequent insults. HSP70 chaperones function in part by driving the molecular triage decision, which determines whether proteins enter the productive folding pathway or result in client substrate ubiquitination and proteasomal degradation. This review examines regulation of losartan-mediated antioxidative stress responses by the chaperone HSP70 in proximal tubule cells of spontaneously hypertensive rats.
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.
Related Concept Videos
Antihypertensive Drugs: Angiotensin II Receptor Blockers
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Drugs: Direct Renin Inhibitors
Renal Drug Excretion: Tubular Secretion
Renal Drug Excretion: Tubular Reabsorption

