Diminished Lipid Raft SNAP23 Increases Blood Pressure by Inhibiting the Membrane Fluidity of Vascular Smooth-Muscle Cells

2015 ◽  
Vol 52 (5) ◽  
pp. 321-333 ◽  
Author(s):  
Mi So Yoon ◽  
Kyung-Jong Won ◽  
Do-Yoon Kim ◽  
Dae Il Hwang ◽  
Seok Won Yoon ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Membrane Fluidity ◽  
Vascular Smooth Muscle Cells ◽  
Lipid Raft ◽  
Muscle Cells

scholarly journals RGS5 Attenuates Baseline Activity of ERK1/2 and Promotes Growth Arrest of Vascular Smooth Muscle Cells

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1748
Author(s):  
Eda Demirel ◽  
Caroline Arnold ◽  
Jaspal Garg ◽  
Marius Andreas Jäger ◽  
Carsten Sticht ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Map Kinase ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Genetic Ablation ◽  
Variable Expression ◽  
Arterial Blood

The regulator of G-protein signaling 5 (RGS5) acts as an inhibitor of Gαq/11 and Gαi/o activity in vascular smooth muscle cells (VSMCs), which regulate arterial tone and blood pressure. While RGS5 has been described as a crucial determinant regulating the VSMC responses during various vascular remodeling processes, its regulatory features in resting VSMCs and its impact on their phenotype are still under debate and were subject of this study. While Rgs5 shows a variable expression in mouse arteries, neither global nor SMC-specific genetic ablation of Rgs5 affected the baseline blood pressure yet elevated the phosphorylation level of the MAP kinase ERK1/2. Comparable results were obtained with 3D cultured resting VSMCs. In contrast, overexpression of RGS5 in 2D-cultured proliferating VSMCs promoted their resting state as evidenced by microarray-based expression profiling and attenuated the activity of Akt- and MAP kinase-related signaling cascades. Moreover, RGS5 overexpression attenuated ERK1/2 phosphorylation, VSMC proliferation, and migration, which was mimicked by selectively inhibiting Gαi/o but not Gαq/11 activity. Collectively, the heterogeneous expression of Rgs5 suggests arterial blood vessel type-specific functions in mouse VSMCs. This comprises inhibition of acute agonist-induced Gαq/11/calcium release as well as the support of a resting VSMC phenotype with low ERK1/2 activity by suppressing the activity of Gαi/o.

Decreased membrane fluidity of erythrocytes and cultured vascular smooth muscle cells in spontaneously hypertensive rats: An electron spin resonance study

1988 ◽  
Vol 75 (5) ◽  
pp. 477-480 ◽  
Author(s):  
Kazushi Tsuda ◽  
Seiko Tsuda ◽  
Yohsuke Minatogawa ◽  
Hideo Iwahashi ◽  
Ryo Kido ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Membrane Fluidity ◽  
Vascular Smooth Muscle Cells ◽  
Spontaneously Hypertensive Rats ◽  
Muscle Cells ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Spin Resonance

1. Membrane fluidity of erythrocytes and cultured vascular smooth muscle cells was studied in spontaneously hypertensive rats (SHR; Okamoto and Aoki strains) by means of an electron spin resonance (e.s.r.) and a spin-label technique. 2. The values of outer hyperfine splitting (2T) and of the order parameter (S) determined from e.s.r. spectra for a fatty acid spin-label agent (5-nitroxy stearate) were significantly higher in erythrocytes of SHR (4 and 10–13 weeks of age) than in those of age-matched Wistar–Kyoto rats (WKY). This finding suggests that the membrane fluidity of erythrocytes might be decreased in SHR. 3. The fluidity of cultured vascular smooth muscle cells obtained from 10-13-week-old SHR was also reduced compared with that from WKY. 4. These results suggest that the decreased membrane fluidity might be a genetically determined abnormality of the cell membranes in SHR.

Abstract 524: Extracellular Guanosine Regulates Extracellular Adenosine Levels

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Edwin K Jackson ◽  
Delbert G Gillespie
Keyword(s):  
Blood Pressure ◽  
Endothelial Cells ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Extracellular Adenosine ◽  
Arterial Blood

Extracellular adenosine modulates cardiovascular and renal function. While measuring extracellular purines in biological samples, we observed a correlation between levels of adenosine and guanosine. This observation led us to test the hypothesis that extracellular guanosine regulates extracellular adenosine levels in the cardiovascular and renal systems. Rat preglomerular vascular smooth muscle cells in culture were incubated with adenosine and/or guanosine. In the absence of added adenosine, exogenous guanosine (30 μmol/L) had little effect on extracellular adenosine levels, indicating that extracellular guanosine does not trigger the release or production of adenosine. Without added guanosine and 1 hour after adding 3 μmol/L of exogenous adenosine, extracellular adenosine levels were only 0.125 ± 0.020 μmol/L, indicating rapid disposition of extracellular adenosine by a monolayer of cells. In contrast, extracellular adenosine levels 1 hour after adding 3 μmol/L of adenosine plus guanosine (30 μmol/L) were 1.173 ± 0.061 μmol/L (9-fold higher; p<0.0001), indicating slow disposition of extracellular adenosine in the presence of extracellular guanosine. Extracellular guanosine impeded the disposition of extracellular adenosine not only in preglomerular vascular smooth muscle cells, but also in rat preglomerular vascular endothelial cells, mesangial cells, cardiac fibroblasts and kidney epithelial cells, as well as in human aortic vascular smooth muscle cells, coronary artery vascular smooth muscle cells and coronary artery endothelial cells. In rats, infusions of guanosine per se had little effect on cardiovascular/renal variables, yet markedly enhanced the effects of co-infusions of adenosine. For example, in control rats, adenosine (0.3 μmol/kg/min) only modestly decreased mean arterial blood pressure (from 114 ± 4 to 100 ± 4 mm Hg). In contrast, in guanosine-treated rats (10 μmol/kg/min), adenosine profoundly decreased blood pressure (from 109 ± 4 to 79 ± 3 mm Hg; p<0.0001 vs non-guanosine treated group). Conclusion: Extracellular guanosine powerfully regulates extracellular adenosine levels by altering adenosine disposition and this occurs in many, perhaps most, cell types in the cardiovascular system and kidneys.

Salt-inducible kinase 1 influences Na+,K+-ATPase activity in vascular smooth muscle cells and associates with variations in blood pressure

2011 ◽  
Vol 29 (12) ◽  
pp. 2395-2403 ◽  
Author(s):  
Sergej Popov ◽  
Angela Silveira ◽  
Dick Wågsäter ◽  
Hiroshi Takemori ◽  
Ryousuke Oguro ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Atpase Activity ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells

scholarly journals High blood pressure associates with the remodelling of inward rectifier K+channels in mice mesenteric vascular smooth muscle cells

2012 ◽  
Vol 590 (23) ◽  
pp. 6075-6091 ◽  
Author(s):  
Sendoa Tajada ◽  
Pilar Cidad ◽  
Alejandro Moreno-Domínguez ◽  
M. Teresa Pérez-García ◽  
José R. López-López
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
High Blood Pressure ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Inward Rectifier ◽  
K Channels

scholarly journals Loss of Chloride Channel 6 (CLC-6) Affects Vascular Smooth Muscle Contractility and Arterial Stiffness via Alterations to Golgi Calcium Stores

Hypertension ◽  
2021 ◽  
Author(s):  
Christine A. Klemens ◽  
Evgeny G. Chulkov ◽  
Jing Wu ◽  
Md Abdul Hye Khan ◽  
Vladislav Levchenko ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Chloride Channel ◽  
Muscle Cells ◽  
Calcium Stores ◽  
Pressure Regulation

Genome-wide association studies have found a number of potential genes involved in blood pressure regulation; however, the functional role of many of these candidates has yet to be established. One such candidate gene is CLCN6 , which encodes the transmembrane protein, chloride channel 6 (ClC-6). Although the CLCN6 locus has been widely associated with human blood pressure regulation, the mechanistic role of ClC-6 in blood pressure homeostasis at the molecular, cellular, and physiological levels is completely unknown. In this study, we demonstrate that rats with a functional knockout of ClC-6 on the Dahl Salt-Sensitive rat background (SS- Clcn6 ) have lower diastolic but not systolic blood pressures. The effect of diastolic blood pressure attenuation was independent of dietary salt exposure in knockout animals. Moreover, SS- Clcn6 rats are protected from hypertension-induced cardiac hypertrophy and arterial stiffening; however, they have impaired vasodilation and dysregulated intracellular calcium handling. ClC-6 is highly expressed in vascular smooth muscle cells where it is targeted to the Golgi apparatus. Using bilayer electrophysiology, we provide evidence that recombinant human ClC-6 protein can function as a channel. Last, we demonstrate that loss of ClC-6 function reduces Golgi calcium stores, which may play a previously unidentified role in vascular contraction and relaxation signaling in vascular smooth muscle cells. Collectively, these data indicate that ClC-6 may modulate blood pressure by regulating Golgi calcium reserves, which in turn contribute to vascular smooth muscle function.

Abstract 1: Deletion of the Mapk-p38 From Vascular Smooth Muscle Cells and Cardiomyocytes Causes Hypotension and Dilated Cardiomyopathy in Angiotensin II Dependent Hypertension

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Susanne Mende ◽  
Katharina Bottermann ◽  
Stefanie Stamer ◽  
Manuel Thieme ◽  
Axel Gödecke ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Dilated Cardiomyopathy ◽  
Vascular Smooth Muscle Cells ◽  
Vascular Injury ◽  
Muscle Cells ◽  
Ang Ii

The heart and the vasculature are key targets of angiotensin (Ang) II. In this regard, Ang II acting via Ang II type 1 (AT1)-receptors induces hypertension, cardiac hypertrophy and vascular injury. Since AT1-receptor stimulation have been shown to activate the mitogen activated protein kinase (MAPK) p38 leading to hypertrophy, migration and remodelling in cardiomocytes and vascular smooth muscle cells (VSMC)s in vitro, the MAPK p38 is considered as a major contributor in Ang II mediated cardiac and vascular injury. In order to investigate its role in Ang II dependent hypertension, we generated mice lacking p38alpha only in VSMC and cardiomyocytes (p38KO) using Cre-Loxp technology with a KISM22-cre transgene on a Bl6/C57 background. The specificity of p38alpha deletion was verified by western blot analysis. While cardiac function did not differ between both groups, blood pressures (BPs) were significantly lower under baseline conditions in p38KO mice compared to controls (106.4±5.2 vs. 123.6±5.4 mmHg; p<0.05). To test whether p38KO mice were protected from hypertensive heart failure and vascular injury, we infused Ang II (1000ng/kg/min) for 2 weeks. Ang II infusion caused a significantly attenuated increase in BPs in p38KOs than in controls (117.9±9.7 vs. 148.0±18.8mmHg; p<0.001). This effect could not be explained by an attenuated vascular response to Ang II in p38KOs, as acute pressor responses to Ang II in vivo and in the isolated perfused kidney as well as changes in renal blood flow were not attenuated in p38KO compared to controls. Surprisingly, in p38KOs, chronic Ang II infusion caused exaggerated cardiac fibrosis and severe dilated cardiomyopathy which was already apparent on day two after Ang II infusion (ejection fraction: 26.6±8.5 (p38KO) vs. 60.8±9.6% (control); p <0.001, diastolic volume: 116.9±8.6 vs. 60.2±7.6μl, p <0.001; systolic volume: 88.9±10.3 vs. 24.6±6.7μl, p <0.001). In summary, these results suggest a divergent role of p38 in regulating blood pressure and in the pathogenesis of heart failure as Ang II induces blood pressure independent dilated cardiomyopathy in p38KO mice. However, more studies are necessary to reveal the underlying mechanism.

scholarly journals The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure

2016 ◽  
Vol 310 (3) ◽  
pp. C193-C204 ◽  
Author(s):  
M. Schepelmann ◽  
P. L. Yarova ◽  
I. Lopez-Fernandez ◽  
T. S. Davies ◽  
S. C. Brennan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Blood Vessel ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Active Phase ◽  
Muscle Cells ◽  
Extracellular Calcium ◽  
Arterial Blood

The extracellular calcium-sensing receptor CaSR is expressed in blood vessels where its role is not completely understood. In this study, we tested the hypothesis that the CaSR expressed in vascular smooth muscle cells (VSMC) is directly involved in regulation of blood pressure and blood vessel tone. Mice with targeted CaSR gene ablation from vascular smooth muscle cells (VSMC) were generated by breeding exon 7 LoxP-CaSR mice with animals in which Cre recombinase is driven by a SM22α promoter (SM22α-Cre). Wire myography performed on Cre-negative [wild-type (WT)] and Cre-positive SM22αCaSRΔflox/Δflox [knockout (KO)] mice showed an endothelium-independent reduction in aorta and mesenteric artery contractility of KO compared with WT mice in response to KCl and to phenylephrine. Increasing extracellular calcium ion (Ca2+) concentrations (1–5 mM) evoked contraction in WT but only relaxation in KO aortas. Accordingly, diastolic and mean arterial blood pressures of KO animals were significantly reduced compared with WT, as measured by both tail cuff and radiotelemetry. This hypotension was mostly pronounced during the animals' active phase and was not rescued by either nitric oxide-synthase inhibition with nitro-l-arginine methyl ester or by a high-salt-supplemented diet. KO animals also exhibited cardiac remodeling, bradycardia, and reduced spontaneous activity in isolated hearts and cardiomyocyte-like cells. Our findings demonstrate a role for CaSR in the cardiovascular system and suggest that physiologically relevant changes in extracellular Ca2+ concentrations could contribute to setting blood vessel tone levels and heart rate by directly acting on the cardiovascular CaSR.

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