scholarly journals 151 Nox5 induces vascular dysfunction and arterial remodelling independently of blood pressure elevation in ang ii-infused nox5-expressing mice

Heart ◽  
2017 ◽  
Vol 103 (Suppl 5) ◽  
pp. A111.1-A111 ◽  
Author(s):  
Augusto Montezano ◽  
Adam Harvey ◽  
Francisco Rios ◽  
Wendy Beatie ◽  
Laura McPherson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Dysfunction ◽  
Ang Ii ◽  
Blood Pressure Elevation ◽  
Pressure Elevation

Angiotensin II induces vascular dysfunction without exacerbating blood pressure elevation in a mouse model of menopause-associated hypertension

2006 ◽  
Vol 24 (7) ◽  
pp. 1365-1373 ◽  
Author(s):  
Danesh Javeshghani ◽  
M Ram Sairam ◽  
Mario Fritsch Neves ◽  
Ernesto L Schiffrin ◽  
Rhian M Touyz
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Mouse Model ◽  
Vascular Dysfunction ◽  
Blood Pressure Elevation ◽  
Pressure Elevation

Abstract 057: Nox5 Induces Vascular Dysfunction and Arterial Remodelling Independently of Blood Pressure Elevation in Ang II-infused Nox5-expressing Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Augusto C Montezano ◽  
Adam P Harvey ◽  
Francisco J Rios ◽  
Maria Dulak-Lis ◽  
Wendy Beatie ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Function ◽  
Kinase Inhibitor ◽  
Vascular Dysfunction ◽  
Rho Kinase ◽  
Lumen Diameter ◽  
Ang Ii ◽  
Cross Sectional ◽  
Blood Pressure Elevation ◽  
Endothelium Dependent Relaxation

Nox5 is a unique Ca 2+ -sensitive Nox isoform that is expressed in human vascular smooth muscle cells (VSMC). Although Nox5 has been implicated in diabetic nephropathy, its role in vascular function and development of hypertension remain unclear. Nox5 is not expressed in rodents, and accordingly we generated humanised Nox5 mice with Nox5 expressed in a VSMC-specific manner (Nox5SM22). Control (wild-type) and Nox5SM22 mice were infused with Ang II (600 ng/Kg/day). Blood pressure (BP) was assessed by tail-cuff. Vascular function and structure of resistance arteries were measured by myography. Ang II increased BP in WT (182.5±10 mmHg) and Nox5SM22 mice (173.1±5 mmHg) with no significant differences. Arteries from Nox5SM22 mice exhibited reduced endothelium-dependent relaxation versus WT controls (%ACh relaxation: 55.1±4 vs ctl: 81.6±7%). Fasudil (Rho kinase inhibitor)-induced relaxation was reduced in Nox5SM22 mice versus controls (%Fas: 111.3±11 vs ctl: 166.6±8%) (p<0.05). Ang II increased the maximal contraction to U46619 (thromboxane A2 mimetic) in WT (115.8±2 vs untreated: 101.4±2%) and Nox5SM22 (121.3±3 vs untreated: 99.1±2) (p<0.05) and induced endothelial dysfunction in all groups. Fasudil-induced relaxation was impaired by Ang II in WT (102.7±6 vs untreated: 166.6±8%, p<0.05) but not further impaired in Nox5SM22 mice (114.9±6 vs untreated: 111.3±11%). Ang II increased cross-sectional area (CSA) and lumen diameter; while in Nox5SM22 mice, Ang II increased wall thickness, wall-to-lumen ratio, CSA and decreased lumen diameter, with associated increased vascular stiffness. Our findings indicate that in mice expressing human Nox5 in VSMCs, endothelium-dependent relaxation is impaired, fasudil-mediated vasodilation is attenuated and vessels undergo exaggerated hypertrophic inward remodelling with increased stiffness; processes that occur independently of BP elevation. These data suggest an important role for Nox5 in Ang II-induced vascular dysfunction and remodeling, but not in the development of hypertension. Moreover, we identify Rho kinase as a putative target for Nox5-induced vascular injury. We provide novel insights into Nox5 vascular biology and demonstrate that vascular Nox5 actions are dissociated from BP effects.

Day- and night-time blood pressure elevation in children with higher grades of renal scarring

2003 ◽  
Vol 142 (2) ◽  
pp. 117-122 ◽  
Author(s):  
Ludwig Patzer ◽  
Tomas Seeman ◽  
Carmen Luck ◽  
Elke Wühl ◽  
Jan Janda ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Scarring ◽  
Night Time ◽  
Blood Pressure Elevation ◽  
Pressure Elevation

Abstract P242: The Role Of Kappa Opioid Receptors In The Development Of Hypertension And Kidney Injury In Sprague-Dawley Rats

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Daria Golosova ◽  
Adrian Zietara ◽  
Ruslan Bohovyk ◽  
Vladislav Levchenko ◽  
Alexander Staruschenko
Keyword(s):  
Blood Pressure ◽  
Sprague Dawley ◽  
Glomerular Injury ◽  
Kappa Opioid ◽  
Injury Score ◽  
Calcium Response ◽  
Blood Pressure Elevation ◽  
Isolated Glomeruli ◽  
Pressure Elevation ◽  
Sd Rats

The extensive use of opioid-based pain management strongly correlates with poor cardiovascular and cardiorenal outcomes. Our recent studies suggest that treatment with kappa opioid receptor (KOR) agonist BRL 52537 leads to the progression of chronic kidney disease (CKD) and aggravation of salt-sensitive hypertension. We hypothesize that stimulation of KORs leads to blood pressure elevation, albuminuria, and kidney damage in healthy Sprague-Dawley (SD) rats. To characterize the effect of the KOR agonist BRL 52537 on the development of blood pressure and kidney function in vivo , SD rats were treated with a daily i.v. bolus infusion of BRL 52537 or a corresponding vehicle. To test the contribution of KOR stimulation on calcium homeostasis in podocytes, BRL 52537 was used on freshly isolated glomeruli from SD rats. Single-channel analysis was applied to assess the effect of KORs stimulation on TRPC6 channel activity in the human immortalized podocytes. Chronic treatment with BRL 52537 leads to increased mean arterial pressure (88±1 vs 101±4 mmHg, vehicle vs treated, p<0.05), podocyte basal calcium (90±12 vs 216±16 a.u., vehicle vs treated, p<0.05), and GFB impairment in SD rats which is reflected by a transient increase in albumin excretion (Alb/cre ratio 0.35±0.1 vs 0.72±0.2, vehicle vs treated, p<0.05). Cumulative probability distribution analysis of the glomerular injury score revealed a rightward shift toward a high glomerular injury score in the group treated with BRL 52537 (p<0.05). Angiotensin II level was higher in a BRL-treated group (156±17 vs 232±59 pmol, vehicle vs treated, p=0.065); however, it did not reach a statistical difference. Acute application of BRL 52537 resulted in sustained calcium response (0.23±0.01 a.u., Fluo4/FuraRed, maximum calcium response) in freshly isolated glomeruli from SD rats. Furthermore, patch-clamp experiments in human immortalized podocytes (cell-attached configuration) revealed that BRL 52537 activated TRPC6 channels. Taken together, these data support the hypothesis that administration of opioids in SD rats leads to activation of the KOR/TRPC6 pathway, which in turn led to glomerular filtration barrier impairment, increased glomerular damage, and blood pressure elevation.

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