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

Rodríguez, Claudia; Sánchez, Ana; Medina, J. Sáenz; Muñoz, Mercedes; Hernández, Medardo; López, Miguel; Rivera, Luis; Contreras, Cristina; Prieto, Dolores

doi:10.1111/bph.15600

Cited by 8 publications

(6 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…AMP-activated protein kinase (AMPK), as a sensor of energy molecules, is closely associated with metabolic stress, diabetes and vascular disorders [ 31 , 32 , 33 , 34 , 35 , 36 ]. In VSMCs, AMPK activation also involves the improvement of oxidative stress, inflammation and calcification [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Adrenomedullin Improves Hypertension and Vascular Remodeling partly through the Receptor-Mediated AMPK Pathway in Rats with Obesity-Related Hypertension

Wang

Chang

et al. 2023

IJMS

View full text Add to dashboard Cite

Adrenomedullin (ADM) is a novel cardiovascular peptide with anti-inflammatory and antioxidant properties. Chronic inflammation, oxidative stress and calcification play pivotal roles in the pathogenesis of vascular dysfunction in obesity-related hypertension (OH). Our study aimed to explore the effects of ADM on the vascular inflammation, oxidative stress and calcification in rats with OH. Eight-week-old Sprague Dawley male rats were fed with either a Control diet or a high fat diet (HFD) for 28 weeks. Next, the OH rats were randomly subdivided into two groups as follows: (1) HFD control group, and (2) HFD with ADM. A 4-week treatment with ADM (7.2 μg/kg/day, ip) not only improved hypertension and vascular remodeling, but also inhibited vascular inflammation, oxidative stress and calcification in aorta of rats with OH. In vitro experiments, ADM (10 nM) in A7r5 cells (rat thoracic aorta smooth muscle cells) attenuated palmitic acid (PA, 200 μM) or angiotensin II (Ang II, 10 nM) alone or their combination treatment-induced inflammation, oxidative stress and calcification, which were effectively inhibited by the ADM receptor antagonist ADM22-52 and AMP-activated protein kinase (AMPK) inhibitor Compound C, respectively. Moreover, ADM treatment significantly inhibited Ang II type 1 receptor (AT1R) protein expression in aorta of rats with OH or in PA-treated A7r5 cells. ADM improved hypertension, vascular remodeling and arterial stiffness, and attenuated inflammation, oxidative stress and calcification in OH state partially via receptor-mediated AMPK pathway. The results also raise the possibility that ADM will be considered for improving hypertension and vascular damage in patients with OH.

show abstract

Section: Discussionmentioning

confidence: 99%

Adrenomedullin Improves Hypertension and Vascular Remodeling partly through the Receptor-Mediated AMPK Pathway in Rats with Obesity-Related Hypertension

Wang

Chang

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Our findings demonstrate that hyperoxaluria induces ED of renal preglomerular arteries in which oxidative stress plays a pivotal role. ED and oxidative stress have been involved in the renal vascular complications of metabolic disorders leading to CKD such as diabetic nephropathy or obesity-associated kidney injury [ 6 , 7 , 20 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Hyperoxaluria Induces Endothelial Dysfunction in Preglomerular Arteries: Involvement of Oxidative Stress

Medina

Muñoz

Rodríguez

et al. 2022

Cells

Self Cite

View full text Add to dashboard Cite

Urolithiasis is a worldwide problem and a risk factor for kidney injury. Oxidative stress-associated renal endothelial dysfunction secondary to urolithiasis could be a key pathogenic factor, similar to obesity and diabetes-related nephropathy. The objective of this paper was to characterize urolithiasis-related endothelial dysfunction in a hyperoxaluria rat model of renal lithiasis. Experimental approach: Characterization of endothelial dysfunction was assessed on preglomerular arteries isolated from control rats and in which 0.75% ethylene glycol was administered in drinking water. Renal interlobar arteries were mounted in microvascular myographs for functional studies; superoxide generation was measured by chemiluminescence and RNAm expression of proteins by RT-PCR and immunofluorescence. Selective inhibitors were used to study the influence of the different ROS sources, xanthine oxidase, COX-2, Nox1, Nox2 and Nox4. Inflammatory vascular response was also studied by measuring the RNAm expression of NF-κB, MCP-1 and TNFα by RT-PCR. Results: Endothelium-dependent vasodilator responses were impaired in the preglomerular arteries of the hyperoxaluric group along with higher superoxide generation in the renal cortex and vascular inflammation developed by MCP-1 and promoted by NF-κB. The xanthine oxidase inhibitor allopurinol restored the endothelial relaxations and returned superoxide generation to basal values. Nox1 and Nox2 mRNA were up-regulated in arteries from the hyperoxaluric group, and Nox1 and Nox2 selective inhibitors also restored the impaired vasodilator responses’ impairment and normalized NADPH oxidase-dependent higher values of the renal cortex from the hyperoxaluric group. Conclusions: The current data support that hyperoxaluria induces oxidative stress-mediated endothelial dysfunction and inflammatory response in renal preglomerular arteries which is promoted by the xanthine oxidase, Nox1 and Nox2 pathways.

show abstract

“…23 Similar experimental evidence supports a direct role of adiponectin, signalling through AMP-kinase in protecting neuronal tissue 24 and kidney 25 from ischaemia-reperfusion injury, supporting the epidemiological evidence from human medicine that associates low plasma adiponectin concentrations with increased risk of stroke in patients suffering acute myocardial infarction. 26 Furthermore, obesity models in mice and rats lead to vascular dysfunction (endothelial dysfunction in particular) related to dysregulation of the AMP-kinase pathway, 27 which has been postulated to partly explain the link between obesity and non-diabetic chronic kidney disease in humans.…”

Section: Hypoxia and Oxidative Stressmentioning

confidence: 99%

Consequences of adiponectin deficiency: Can they be related to the pathophysiology of laminitis?

Elliott

Bailey

2023

Equine Veterinary Journal

View full text Add to dashboard Cite

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

Cited by 8 publications

References 75 publications

Adrenomedullin Improves Hypertension and Vascular Remodeling partly through the Receptor-Mediated AMPK Pathway in Rats with Obesity-Related Hypertension

Adrenomedullin Improves Hypertension and Vascular Remodeling partly through the Receptor-Mediated AMPK Pathway in Rats with Obesity-Related Hypertension

Hyperoxaluria Induces Endothelial Dysfunction in Preglomerular Arteries: Involvement of Oxidative Stress

Consequences of adiponectin deficiency: Can they be related to the pathophysiology of laminitis?

Contact Info

Product

Resources

About