Activation of AMP kinase ameliorates kidney vascular dysfunction, oxidative stress and inflammation in rodent models of obesity



Downloads per month over past year

Rodríguez Prados, Claudia and Sánchez Pina, Ana Alejandra and Sáenz Medina, Javier and Muñoz Picos, Mercedes and Hernández Rodríguez, Medardo Vicente and López, Miguel and Rivera de los Arcos, Luis and Contreras Jiménez, Cristina and Prieto Ocejo, Dolores (2021) Activation of AMP kinase ameliorates kidney vascular dysfunction, oxidative stress and inflammation in rodent models of obesity. British Journal of Pharmacology, 178 (20). pp. 4085-4103. ISSN 0007-1188

[thumbnail of British J Pharmacology - 2021 - Rodr guez - Activation of AMP kinase amel.pdf]
Creative Commons Attribution Non-commercial No Derivatives.


Official URL:


Background and Purpose
Obesity is a risk factor for the development of chronic kidney disease independent of diabetes, hypertension and other co-morbidities. Obesity-associated nephropathy is linked to dysregulation of the cell energy sensor AMP-activated protein kinase (AMPK). We aimed here to assess whether impairment of AMPK activity may cause renal arterial dysfunction in obesity and to evaluate the therapeutic potential of activating renal AMPK.
Experimental Approach
Effects of the AMPK activator A769662 were assessed on intrarenal arteries isolated from ob/ob mice and obese Zucker rats and then mounted in microvascular myographs. Superoxide and hydrogen peroxide production were measured by chemiluminescence and fluorescence, respectively, and protein expression was analysed by western blotting.
Key Results
Endothelium-dependent vasodilation and PI3K/Akt/eNOS pathway were impaired in preglomerular arteries from genetically obese rats and mice, along with impaired arterial AMPK activity and blunted relaxations induced by the AMPK activator A769662. Acute ex vivo exposure to A769662 restored endothelial function and enhanced activity of PI3K/Akt/eNOS pathway in obese rats, whereas in vivo treatment with A769662 improved metabolic state and ameliorated endothelial dysfunction, reduced inflammatory markers and vascular oxidative stress in renal arteries and restored redox balance in renal cortex of obese mice.
Conclusion and Implications
These results demonstrate that AMPK dysregulation underlies obesity-associated kidney vascular dysfunction and activation of AMPK improves metabolic state, protects renal endothelial function and exerts potent vascular antioxidant and anti-inflammatory effects. The beneficial effects of vascular AMPK activation might represent a promising therapeutic approach to the treatment of obesity-related kidney injury.

Item Type:Article
Additional Information:

CRUE-CSIC (Acuerdos Transformativos 2021)

Uncontrolled Keywords:AMPK; Endothelial dysfunction; Inflammation; Kidney; Oobesity; Oxidative stress
Subjects:Medical sciences > Medicine > Physiology
Medical sciences > Medicine > Nephrology and Urology
Medical sciences > Pharmacy > Animal physiology
ID Code:70475
Deposited On:15 Feb 2022 12:12
Last Modified:21 Feb 2022 15:20

Origin of downloads

Repository Staff Only: item control page