Delineating the receptor mechanisms underlying the rapid vascular contractile effects of aldosterone and estradiol

2011 ◽  
Vol 89 (9) ◽  
pp. 655-663 ◽  
Author(s):  
Robert Gros ◽  
Qingming Ding ◽  
Mark Davis ◽  
Rasha Shaikh ◽  
Bonan Liu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Mineralocorticoid Receptor ◽  
Time Course ◽  
Cardiovascular Effects ◽  
Muscle Cells ◽  
Smooth Muscle Contraction ◽  
Cell Assays

It is increasingly appreciated that steroid hormones such as aldosterone and estradiol can mediate important cardiovascular effects. Many of these effects occur over a time course not consistent with the genomic actions of these hormones acting through classical nuclear receptors / transcription factors. Further, multiple receptors have been implicated in mediating these rapid effects of both aldosterone and estradiol, including a newly appreciated G-protein-coupled receptor, GPR30. In previous studies we demonstrated that both aldosterone and estradiol mediate contraction in vascular smooth muscle cells, as assessed in single cell assays. However, the receptor mechanisms underlying these effects remained unclear. Therefore, we studied the actions of estradiol and aldosterone on rat aortic vascular smooth muscle cells. Both aldosterone and estradiol mediated a concentration-dependent increase in contraction, as assessed in substrate deformation assays with EC50s in the range of nanomoles per litre. These effects paralleled increased myosin light chain phosphorylation. The effects of aldosterone were inhibited by the mineralocorticoid selective antagonist eplerenone. Further, aldosterone’s contractile effects were enhanced by increased expression of the mineralocorticoid receptor. The contractile effects of estradiol were inhibited by estrogen receptor (ER)-selective antagonists, tamoxifen, and ICI 182780, as well as eplerenone. Further, estradiol’s effects were enhanced by the increased expression of both ERα and the mineralocorticoid receptor (MR). To assess the potential role of GPR30 in mediating the effects of aldosterone and estradiol, GPR30 was re-introduced, since these cells lose endogenous GPR30 expression in culture. Re-expression of GPR30 enhanced both estradiol- and aldosterone-mediated contraction. These studies demonstrate that in rat aortic vascular smooth muscle cells, both aldosterone and estradiol mediate vascular smooth muscle contraction and that these effects can be mediated by MR, ERα, and by GPR30.

Spatial dynamics of intracellular calcium in agonist-stimulated vascular smooth muscle cells

1990 ◽  
Vol 259 (4) ◽  
pp. C675-C686 ◽  
Author(s):  
C. B. Neylon ◽  
J. Hoyland ◽  
W. T. Mason ◽  
R. F. Irvine
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Vascular Tissue ◽  
Spatial Dynamics ◽  
Muscle Cells ◽  
Smooth Muscle Contraction ◽  
The Novel ◽  
Internal Mammary

Vasoconstrictor agonists stimulate smooth muscle contraction by inducing a rise in intracellular free Ca2+. Digital-imaging microscopy of fura-2 fluorescence from single vascular smooth muscle cells cultured from the human internal mammary artery has allowed us to record the subcellular alterations in Ca2+ that occur immediately after stimulation by receptor agonists. The thrombin-induced rise in cytoplasmic free Ca2+ begins in a discrete region typically located close to the end of the cell. Subsequently, this region of elevated Ca2+ expands until Ca2+ is elevated throughout the cell cytoplasm. The rate of spreading in the region of elevated Ca2+ in a linear direction averaged 10.1 microns/s, enabling it to traverse the length of most cells within approximately 5 s, and involved rises in Ca2+ of between 200 and 500 nM. In some cells, the Ca2+ rise began at both ends and collided midway. Similar dynamic changes in the spatial distribution of Ca2+ were recorded in cells stimulated by acetylcholine. The novel observation that vasoconstrictor agonists induce an elevation of Ca2+ in a localized region which subsequently expands throughout the cytoplasm of single smooth muscle cells may provide new insight into the nature of Ca2+ signaling in vascular tissue.

Cocaine Induces Apoptosis in Primary Cultured Rat Aortic Vascular Smooth Muscle Cells: Possible Relationship to Aortic Dissection, Atherosclerosis, and Hypertension

2004 ◽  
Vol 23 (4) ◽  
pp. 233-237 ◽  
Author(s):  
Jialin Su ◽  
Jianfeng Li ◽  
Wenyan Li ◽  
Bella T. Altura ◽  
Burton M. Altura
Keyword(s):  
Smooth Muscle ◽  
Aortic Dissection ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Cocaine Abuse ◽  
Cardiovascular Effects ◽  
Muscle Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner

Cocaine abuse is known to induce many adverse cardiovascular effects, including hypertension, atherosclerosis, and aortic dissection. A major physiological event leading to these pathophysiological actions of cocaine could be apoptosis. This study was designed to investigate if primary cultured rat aortic vascular smooth muscle cells (VSMCs) can undergo apoptosis when treated with cocaine. After treatment with cocaine (10−6 to 10−4 M), morphological analysis of aortic VSMCs using confocal fluoresence microscopy showed that the percentage of apoptotic aortic VSMCs increased after cocaine (10−6 to 10−4 M) treatment for 12, 24, and 48 h. These results demonstrate that aortic VSMCs can undergo rapid apoptosis in response to cocaine in a concentration-dependent manner. Cocaine-induced apoptosis may thus play a major role in cocaine abuse-induced aortic dissection, atherosclerosis, and hypertension.

Tyrosine phosphorylation and association of p130Cas and c-Crk II by ANG II in vascular smooth muscle cells

1998 ◽  
Vol 274 (4) ◽  
pp. H1059-H1065 ◽  
Author(s):  
Tomosaburo Takahashi ◽  
Yasuhiro Kawahara ◽  
Takahiro Taniguchi ◽  
Mitsuhiro Yokoyama
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Tyrosine Phosphorylation ◽  
Vascular Smooth Muscle Cells ◽  
Time Course ◽  
Muscle Cells ◽  
Ang Ii ◽  
Acetoxymethyl Ester ◽  
Specific Association

In cultured vascular smooth muscle cells (VSMC), angiotensin II (ANG II) stimulated tyrosine phosphorylation of multiple proteins including a 130-kDa protein. This 130-kDa protein was identified as a Crk-associated substrate, p130Cas. ANG II-stimulated tyrosine phosphorylation of p130Cas was rapid, concentration dependent, and inhibited by the AT1-receptor antagonist CV-11974. Neither downregulation of protein kinase C by long exposure of cells to phorbol 12,13-dibutyrate nor blockade of Ca2+ mobilization by 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid acetoxymethyl ester had an effect on ANG II-stimulated tyrosine phosphorylation of p130Cas. Stimulation with ANG II enhanced the specific association of p130Cas with c-Crk II. The time course of the association of p130Cas and c-Crk II was similar to that of tyrosine phosphorylation of p130Cas. c-Crk II was also tyrosine phosphorylated in response to ANG II. These results indicate that ANG II induces tyrosine phosphorylation of p130Cas and c-Crk II and their specific association, suggesting a potential role of the p130Cas-c-Crk II complex in ANG II signal transduction in VSMC.

scholarly journals Mineralocorticoid Receptor in Calcium Handling of Vascular Smooth Muscle Cells

2018 ◽  
Author(s):  
Rogelio Salazar-Enciso ◽  
Nohemi A. Camacho-Concha ◽  
Thassio R. Mesquita ◽  
Débora Falcón ◽  
Jean-Pierre Benitah ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Mineralocorticoid Receptor ◽  
Muscle Cells ◽  
Calcium Handling

Continuous membrane voltage recordings in A10 vascular smooth muscle cells: effect of AVP

1989 ◽  
Vol 257 (2) ◽  
pp. C323-C332 ◽  
Author(s):  
C. Korbmacher ◽  
H. Helbig ◽  
F. Stahl ◽  
M. Coroneo ◽  
H. Haller ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Action Potentials ◽  
Time Course ◽  
Calcium Transient ◽  
Muscle Cells ◽  
Membrane Voltage ◽  
Voltage Response

Continuous membrane voltage (V) recordings were obtained in A10 vascular smooth muscle cells (rat aorta) using glass microelectrodes. Resting membrane voltage in 262 impalements averaged 54.0 +/- 0.4 (SE) mV. Relative K+ conductance was characterized, and the contribution of electrogenic Na+-K+-ATPase to membrane voltage was investigated. Action potentials could be induced by application of 1 mM barium or 10(-4) M acetylcholine. In a few recordings, spontaneous spike activity occurred, and this could be abolished by 5 mM MgCl2 or by removal of extracellular Ca2+. Barium-induced action potentials were not dependent on the presence of extracellular Na+ and not inhibitable by 10(-6) M tetrodotoxin. Application of 10(-6) M [Arg8] vasopressin (AVP) for 30 s caused a typical biphasic membrane voltage response with an initial transient hyperpolarization of -9.5 +/- 1.1 mV and a more sustained subsequent depolarizing response averaging 28.2 +/- 1.3 mV (mean +/- SE, n = 58). The effect of AVP on membrane voltage was blocked by the V1-antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropionyl1,O-Me- Tyr2,Arg8]vasopressin. The initial hyperpolarizing component of the membrane voltage response to AVP became more prominent when V was predepolarized, for example, by a preceding AVP application. However, when AVP was applied during high K+ depolarization or in the presence of quinidine (1 mM), the initial hyperpolarizing response was practically abolished. The time course of the initial hyperpolarization was shown to be similar to the calcium transient observed in fura-2-loaded A10 cell suspensions after the application of AVP. We conclude that the initial AVP-induced hyperpolarization in A10 cells corresponds to an activation of Ca2+-activated K+ channels.

Activated mineralocorticoid receptor regulates micro‐RNA‐29b in vascular smooth muscle cells

2016 ◽  
Vol 30 (4) ◽  
pp. 1610-1622 ◽  
Author(s):  
Maria Bretschneider ◽  
Bianca Busch ◽  
Daniel Mueller ◽  
Alexander Nolze ◽  
Barbara Schreier ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Mineralocorticoid Receptor ◽  
Muscle Cells ◽  
Micro Rna

Isoflurane Pretreatment Has Immediate and Delayed Protective Effects against Cytokine-induced Injury in Endothelial and Vascular Smooth Muscle Cells

2003 ◽  
Vol 99 (4) ◽  
pp. 896-903 ◽  
Author(s):  
Manuela J. M. de Klaver ◽  
Mary-Gordon Buckingham ◽  
George F. Rich
Keyword(s):  
Smooth Muscle ◽  
Potassium Channels ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Adenosine Triphosphate ◽  
Vascular Smooth Muscle Cells ◽  
Time Course ◽  
Muscle Cells ◽  
Protective Effects ◽  
Lactate Dehydrogenase Release

Background Volatile anesthetics have protective effects against cytokine-induced injury in endothelial and vascular smooth muscle cells. The authors hypothesized that isoflurane pretreatment may trigger immediate and delayed protection that is modulated by adenosine triphosphate-sensitive potassium channels. Methods Human and bovine endothelial cells and rat vascular smooth muscle cells were pretreated with isoflurane (1.5% for 30 min) and then exposed to cytokines (tumor necrosis factor-alpha, interferon-gamma, and interleukin-beta) for 72 h. Cytokine exposure was initiated immediately after isoflurane pretreatment or after a delay of 1-48 h. Cell survival and viability were evaluated by trypan blue exclusion and lactate dehydrogenase release. The role of mitochondrial and cell membrane adenosine triphosphate-sensitive potassium channels, or both, were evaluated with the antagonists 5-hydroxydecanoate, HMR-1098, or glybenclamide. Results Immediate isoflurane pretreatment was approximately 70% effective in increasing cell survival and prevented lactate dehydrogenase release in all cell lines. However, cellular protection was completely lost if the time between isoflurane and cytokine exposure was extended to 2-12 h, depending on the cell type. Delayed protection was equal to immediate protection when the interval was extended to 12-24 h, with protection being sustained at 48 h in human endothelial and rat vascular smooth muscle cells. The immediate and delayed protection was inhibited by glybenclamide and 5-hydroxydecanoate but not by HMR-1098, whereas diazoxide, a mitochondrial adenosine triphosphate-sensitive potassium channels agonist, mimicked the time course of isoflurane-induced immediate and delayed protection in all cell lines. Conclusion Isoflurane pretreatment has immediate and delayed protective effects against cytokine-induced injury in endothelial and vascular smooth muscle cells that seem to be modulated by mitochondrial adenosine triphosphate-sensitive potassium channels. The time course of immediate and delayed protection is similar but not identical for each cell type.

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