scholarly journals P705Downregulation of vascular smooth muscle GRK2 expression promotes functional and biochemical alterations in a mouse model of hypertension

2014 ◽  
Vol 103 (suppl 1) ◽  
pp. S129.2-S129
Author(s):  
E Tutunea-Fatan ◽  
R Gros ◽  
F Caetano ◽  
S Ferguson
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Vascular Smooth Muscle ◽  
Biochemical Alterations ◽  
Grk2 Expression

scholarly journals Pressure-induced constriction is inhibited in a mouse model of reduced βENaC

2009 ◽  
Vol 297 (3) ◽  
pp. R723-R728 ◽  
Author(s):  
Lauren G. VanLandingham ◽  
Kimberly P. Gannon ◽  
Heather A. Drummond
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Cerebral Arteries ◽  
Muscle Cells ◽  
Normal Pressure ◽  
Quantitative Immunofluorescence ◽  
Mechanosensitive Ion Channel

Recent studies suggest certain epithelial Na+channel (ENaC) proteins may be components of mechanosensitive ion channel complexes in vascular smooth muscle cells that contribute to pressure-induced constriction in middle cerebral arteries (MCA). However, the role of a specific ENaC protein, βENaC, in pressure-induced constriction of MCAs has not been determined. The goal of this study was to determine whether pressure-induced constriction in the MCA is altered in a mouse model with reduced levels of βENaC. Using quantitative immunofluorescence, we found whole cell βENaC labeling in cerebral vascular smooth muscle cells (VSMCs) was suppressed 46% in βENaC homozygous mutant (m/m) mice compared with wild-type littermates (+/+). MCAs from βENaC +/+ and m/m mice were isolated and placed in a vessel chamber for myographic analysis. Arteries from βENaC+/+ mice constricted to stepwise increases in perfusion pressure and developed maximal tone of 10 ± 2% at 90 mmHg ( n = 5). In contrast, MCAs from βENaC m/m mice developed significantly less tone (4 ± 1% at 90 mmHg, n = 5). Vasoconstrictor responses to KCl (4–80 mM) were identical between genotypes and responses to phenylephrine (10−7-10−4M) were marginally altered, suggesting that reduced levels of VSMC βENaC specifically inhibit pressure-induced constriction. Our findings indicate βENaC is required for normal pressure-induced constriction in the MCA and provide further support for the hypothesis that βENaC proteins are components of a mechanosensor in VSMCs.

Augmented Contractile Response of Vascular Smooth Muscle in a Diabetic Mouse Model

2003 ◽  
Vol 40 (6) ◽  
pp. 520-530 ◽  
Author(s):  
Elena B. Okon ◽  
Tania Szado ◽  
Ismail Laher ◽  
Bruce McManus ◽  
Cornelis van Breemen
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Vascular Smooth Muscle ◽  
Contractile Response ◽  
Diabetic Mouse

scholarly journals Phenotypic Alteration of Vascular Smooth Muscle Cells Precedes Elastolysis in a Mouse Model of Marfan Syndrome

2001 ◽  
Vol 88 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Tracie E. Bunton ◽  
Nancy Jensen Biery ◽  
Loretha Myers ◽  
Barbara Gayraud ◽  
Francesco Ramirez ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Marfan Syndrome ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Phenotypic Alteration

scholarly journals EP3 (E-Prostanoid 3) Receptor Mediates Impaired Vasodilation in a Mouse Model of Salt-Sensitive Hypertension

Hypertension ◽  
2021 ◽  
Author(s):  
Jing Wu ◽  
Shi Fang ◽  
Ko-Ting Lu ◽  
Kelsey Wackman ◽  
Michal L. Schwartzman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Mouse Model ◽  
Vascular Smooth Muscle ◽  
Rho Kinase ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Renal Vessels ◽  
Salt Sensitive Hypertension

We previously showed that impaired vasodilation in systemic and renal vessels contributes to salt-sensitive hypertension in a mouse model of impaired PPARγ (peroxisome proliferator-activated receptor gamma) function. We determined the mechanisms mediating impaired salt-induced vasodilation and whether improved vasodilation attenuates augmented hypertension in response to salt. Mice selectively expressing a PPARγ dominant negative mutation in vascular smooth muscle (S-P467L) exhibited salt-sensitive hypertension and severely impaired vasodilation in systemic and renal vessels. High-salt diet–fed S-P467L and control mice displayed comparable levels of renal oxidative stress markers. Preincubation with Tempol, a superoxide dismutase mimetic, or calphostin C, a PKC (protein kinase C) inhibitor, failed to improve salt-induced impairment of vasodilation in S-P467L mice, arguing against a role of oxidative stress or PKC activity. Inhibition of Rho kinase partially rescued impaired vasodilation in high-salt diet–fed S-P467L mice suggesting a contribution of the Ras homolog family member A (RhoA)/Rho kinase pathway. High-salt diet selectively increased synthesis of PGE2 (prostaglandin E2) in S-P467L aorta. Expression of EP3 (E-prostanoid 3) receptor mRNA was increased in aorta from chow-fed and high salt–fed S-P467L mice. Pharmacological inhibition of COX (cyclooxygenase) 2 or blockade of EP3 completely normalized the impaired vasodilation, and EP3 antagonism induced larger decreases in systolic blood pressure in high-salt diet–fed S-P467L mice. In conclusion, interference with PPARγ in vascular smooth muscle causes activation of the PGE2/EP3 signaling pathway in systemic and renal vasculature resulting in salt-induced impairment of vasodilation and salt-sensitive hypertension. PGE2/EP3 axis maybe a druggable target to prevent salt-sensitive hypertension in chronic conditions associated with decreased PPARγ activity.

scholarly journals Vascular Smooth Muscle Cell-Specific Progerin Expression Provokes Contractile Impairment in a Mouse Model of Hutchinson-Gilford Progeria Syndrome that Is Ameliorated by Nitrite Treatment

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 656 ◽  
Author(s):  
Lara del Campo ◽  
Amanda Sánchez-López ◽  
Cristina González-Gómez ◽  
María Jesús Andrés-Manzano ◽  
Beatriz Dorado ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Endothelial Dysfunction ◽  
Mouse Model ◽  
Vascular Smooth Muscle ◽  
Vascular Tone ◽  
Genetic Disorder ◽  
Cell Types ◽  
Dietary Sodium ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

Cardiovascular disease (CVD) is the main cause of death worldwide, and aging is its leading risk factor. Aging is much accelerated in Hutchinson–Gilford progeria syndrome (HGPS), an ultra-rare genetic disorder provoked by the ubiquitous expression of a mutant protein called progerin. HGPS patients die in their teens, primarily due to cardiovascular complications. The primary causes of age-associated CVD are endothelial dysfunction and dysregulated vascular tone; however, their contribution to progerin-induced CVD remains poorly characterized. In the present study, we found that progeroid LmnaG609G/G609G mice with ubiquitous progerin expression show both endothelial dysfunction and severe contractile impairment. To assess the relative contribution of specific vascular cell types to these anomalies, we examined LmnaLCS/LCSTie2Cretg/+ and LmnaLCS/LCSSm22αCretg/+ mice, which express progerin specifically in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), respectively. Whereas vessel contraction was impaired in mice with VSMC-specific progerin expression, we observed no endothelial dysfunction in mice with progerin expression restricted to VSMCs or ECs. Vascular tone regulation in progeroid mice was ameliorated by dietary sodium nitrite supplementation. Our results identify VSMCs as the main cell type causing contractile impairment in a mouse model of HGPS that is ameliorated by nitrite treatment.

scholarly journals Attenuation of Chondrogenic Transformation in Vascular Smooth Muscle by Dietary Quercetin in the MGP-Deficient Mouse Model

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e76210 ◽  
Author(s):  
Kelly E. Beazley ◽  
Florence Lima ◽  
Teresa Borras ◽  
Maria Nurminskaya
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Vascular Smooth Muscle ◽  
Deficient Mouse
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