scholarly journals Soluble (Pro)Renin Receptor Induces Endothelial Dysfunction and Hypertension in Mice with Diet-Induced Obesity via Activation of AngiotensinII Type 1 Receptor

2021 ◽  
Author(s):  
Ziwei Fu ◽  
Fei Wang ◽  
Xiyang Liu ◽  
Jiajia Hu ◽  
Jiahui Su ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Umbilical Vein ◽  
Elevated Blood Pressure ◽  
H2o2 Production ◽  
No Production ◽  
Ang Ii ◽  
Elevated Blood ◽  
Diet Induced Obesity

Until now, renin-angiotensin system (RAS) hyperactivity was largely thought to result from angiotensin II (Ang II) dependent stimulation of the Ang II type 1 receptor (AT1R). Here we assessed the role of soluble (pro)renin receptor (sPRR), a product of site-1 protease-mediated cleavage of (pro)renin receptor (PRR), as a possible ligand of the AT1R in mediating: (i) endothelial cell dysfunction in vitro; and (ii) arterial dysfunction in mice with diet-induced obesity. Primary human umbilical vein endothelial cells (HUVECs) treated with a recombinant histidine-tagged sPRR (sPRR-His) exhibited IκBα degradation concurrent with NF-κB p65 activation. These responses were secondary to sPRR-His evoked elevations in Nox4-derived H2O2 production that resulted in inflammation, apoptosis and reduced NO production. Each of these sPRR-His-evoked responses was attenuated by AT1R inhibition using Losartan (Los) but not ACE inhibition using captopril (Cap). Further mechanistic exploration revealed that sPRR-His activated AT1R downstream Gq signaling pathway. Immunoprecipitation coupled with autoradiography experiments and radioactive ligand competitive binding assays indicate sPRR directly interacts with AT1R via Lysine199 and Asparagine295. Important translational relevance was provided by findings from obese C57/BL6 mice that sPRR-His evoked endothelial dysfunction was sensitive to Los. Besides, sPRR-His elevated blood pressure in obese C57/BL6 mice, an effect that was reversed by concurrent treatment with Los but not Cap. Collectively, we provide solid evidence that the AT1R mediates the functions of sPRR during obesity-related hypertension. Inhibiting sPRR signaling should be considered further as a potential therapeutic intervention in the treatment and prevention of cardiovascular disorders involving elevated blood pressure.

scholarly journals Na+-sensitive elevation in blood pressure is ENaC independent in diet-induced obesity and insulin resistance

2016 ◽  
Vol 310 (9) ◽  
pp. F812-F820 ◽  
Author(s):  
Jonathan M. Nizar ◽  
Wuxing Dong ◽  
Robert B. McClellan ◽  
Mariana Labarca ◽  
Yuehan Zhou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
High Fat ◽  
Electrolyte Excretion ◽  
Diet Induced Obesity ◽  
Collecting Ducts ◽  
Fat Feeding

The majority of patients with obesity, insulin resistance, and metabolic syndrome have hypertension, but the mechanisms of hypertension are poorly understood. In these patients, impaired sodium excretion is critical for the genesis of Na+-sensitive hypertension, and prior studies have proposed a role for the epithelial Na+ channel (ENaC) in this syndrome. We characterized high fat-fed mice as a model in which to study the contribution of ENaC-mediated Na+ reabsorption in obesity and insulin resistance. High fat-fed mice demonstrated impaired Na+ excretion and elevated blood pressure, which was significantly higher on a high-Na+ diet compared with low fat-fed control mice. However, high fat-fed mice had no increase in ENaC activity as measured by Na+ transport across microperfused cortical collecting ducts, electrolyte excretion, or blood pressure. In addition, we found no difference in endogenous urinary aldosterone excretion between groups on a normal or high-Na+ diet. High fat-fed mice provide a model of metabolic syndrome, recapitulating obesity, insulin resistance, impaired natriuresis, and a Na+-sensitive elevation in blood pressure. Surprisingly, in contrast to previous studies, our data demonstrate that high fat feeding of mice impairs natriuresis and produces elevated blood pressure that is independent of ENaC activity and likely caused by increased Na+ reabsorption upstream of the aldosterone-sensitive distal nephron.

scholarly journals Renal Natriuretic Peptide Receptor-C Deficiency Attenuates NaCl Cotransporter Activity in Angiotensin II–Induced Hypertension

Hypertension ◽  
2021 ◽  
Vol 77 (3) ◽  
pp. 868-881
Author(s):  
Shuai Shao ◽  
Xiao-Dong Li ◽  
Yuan-Yuan Lu ◽  
Shi-Jin Li ◽  
Xiao-Hui Chen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Natriuretic Peptide ◽  
Elevated Blood Pressure ◽  
Natriuretic Peptide Receptor ◽  
Sodium Retention ◽  
Ang Ii ◽  
Elevated Blood ◽  
Peptide Receptor ◽  
Induced Hypertension

Genome-wide association studies have identified that NPR-C (natriuretic peptide receptor-C) variants are associated with elevation of blood pressure. However, the mechanism underlying the relationship between NPR-C and blood pressure regulation remains elusive. Here, we investigate whether NPR-C regulates Ang II (angiotensin II)-induced hypertension through sodium transporters activity. Wild-type mice responded to continuous Ang II infusion with an increased renal NPR-C expression. Global NPR-C deficiency attenuated Ang II–induced increased blood pressure both in male and female mice associated with more diuretic and natriuretic responses to a saline challenge. Interestingly, Ang II increased both total and phosphorylation of NCC (NaCl cotransporter) abundance involving in activation of WNK4 (with-no-lysine kinase 4)/SPAK (Ste20-related proline/alanine-rich kinase) which was blunted by NPR-C deletion. NCC inhibitor, hydrochlorothiazide, failed to induce natriuresis in NPR-C knockout mice. Moreover, low-salt and high-salt diets–induced changes of total and phosphorylation of NCC expression were normalized by NPR-C deletion. Importantly, tubule-specific deletion of NPR-C also attenuated Ang II–induced elevated blood pressure, total and phosphorylation of NCC expression. Mechanistically, in distal convoluted tubule cells, Ang II dose and time-dependently upregulated WNK4/SPAK/NCC kinase pathway and NPR-C/Gi/PLC/PKC signaling pathway mediated NCC activation. These results demonstrate that NPR-C signaling regulates NCC function contributing to sodium retention-mediated elevated blood pressure, which suggests that NPR-C is a promising candidate for the treatment of sodium retention-related hypertension.

Improving the Recognition and Management of Elevated Blood Pressure among Youth with Type 1 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1307-P
Author(s):  
KAJAL GANDHI ◽  
DON A. BUCKINGHAM ◽  
JESSICA HEHMEYER ◽  
ALYSSA M. KRAMER ◽  
KATHRYN OBRYNBA ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 1 Diabetes ◽  
Elevated Blood Pressure ◽  
Elevated Blood

scholarly journals Endothelial Dysfunction and Elevated Blood Pressure in Mas Gene-Deleted Mice

Hypertension ◽  
2008 ◽  
Vol 51 (2) ◽  
pp. 574-580 ◽  
Author(s):  
Ping Xu ◽  
Andrey C. Costa-Goncalves ◽  
Mihail Todiras ◽  
Luiza A. Rabelo ◽  
Walkyria O. Sampaio ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Elevated Blood Pressure ◽  
Elevated Blood

055 Elevated blood pressure in offspring born to hypertensive pregnancy: is endothelial dysfunction the underlying vascular mechanism?

Heart ◽  
2010 ◽  
Vol 96 (Suppl 1) ◽  
pp. A33-A34
Author(s):  
M Lazdam ◽  
A Pitcher ◽  
A de la Horra ◽  
I Kylintireas ◽  
Z Mannie ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Hypertensive Pregnancy

Dietary restriction but not angiotensin II type 1 receptor blockade improves DNA damage-related vasodilator dysfunction in rapidly aging Ercc1Δ/− mice

2017 ◽  
Vol 131 (15) ◽  
pp. 1941-1953 ◽  
Author(s):  
Haiyan Wu ◽  
Bibi S. van Thiel ◽  
Paula K. Bautista-Niño ◽  
Erwin Reiling ◽  
Matej Durik ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Dna Damage ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Dietary Restriction ◽  
Organ Bath ◽  
Receptor Blockade ◽  
Ang Ii ◽  
No Signaling

DNA damage is an important contributor to endothelial dysfunction and age-related vascular disease. Recently, we demonstrated in a DNA repair-deficient, prematurely aging mouse model (Ercc1Δ/− mice) that dietary restriction (DR) strongly increases life- and health span, including ameliorating endothelial dysfunction, by preserving genomic integrity. In this mouse mutant displaying prominent accelerated, age-dependent endothelial dysfunction we investigated the signaling pathways involved in improved endothelium-mediated vasodilation by DR, and explore the potential role of the renin-angiotensin system (RAS). Ercc1Δ/− mice showed increased blood pressure and decreased aortic relaxations to acetylcholine (ACh) in organ bath experiments. Nitric oxide (NO) signaling and phospho-Ser1177-eNOS were compromised in Ercc1Δ/−. DR improved relaxations by increasing prostaglandin-mediated responses. Increase of cyclo-oxygenase 2 and decrease of phosphodiesterase 4B were identified as potential mechanisms. DR also prevented loss of NO signaling in vascular smooth muscle cells and normalized angiotensin II (Ang II) vasoconstrictions, which were increased in Ercc1Δ/− mice. Ercc1Δ/− mutants showed a loss of Ang II type 2 receptor-mediated counter-regulation of Ang II type 1 receptor-induced vasoconstrictions. Chronic losartan treatment effectively decreased blood pressure, but did not improve endothelium-dependent relaxations. This result might relate to the aging-associated loss of treatment efficacy of RAS blockade with respect to endothelial function improvement. In summary, DR effectively prevents endothelium-dependent vasodilator dysfunction by augmenting prostaglandin-mediated responses, whereas chronic Ang II type 1 receptor blockade is ineffective.

TRAF3IP2 ablation protects against obesity‐associated glycemic dysregulation, elevated blood pressure, and endothelial dysfunction

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Zachary Ian Grunewald ◽  
Makenzie L. Woodford ◽  
Francisco I. Ramirez-Perez ◽  
Mariana Morales-Quinones ◽  
Camila Manrique-Acevedo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Elevated Blood Pressure ◽  
Elevated Blood

scholarly journals Elevated Blood Pressure in Adolescent Boys Predicts Endothelial Dysfunction

Hypertension ◽  
2006 ◽  
Vol 48 (3) ◽  
pp. 424-430 ◽  
Author(s):  
Markus Juonala ◽  
Jorma S.A. Viikari ◽  
Tapani Rönnemaa ◽  
Hans Helenius ◽  
Leena Taittonen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Adolescent Boys

High prevalence of elevated blood pressure among children with neurofibromatosis type 1

2015 ◽  
Vol 31 (1) ◽  
pp. 131-136 ◽  
Author(s):  
Tom Dubov ◽  
Hagit Toledano-Alhadef ◽  
Gil Chernin ◽  
Shlomi Constantini ◽  
Roxana Cleper ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
High Prevalence
Sign in / Sign up

Export Citation Format

Share Document