Chronic elevated endothelin-1 concentrations regulate mitogen-activated protein kinases ERK 1 and ERK 2 in vascular smooth muscle cells

2002 ◽  
Vol 103 (s2002) ◽  
pp. 137S-140S ◽  
Author(s):  
Bernhard R. BREHM ◽  
Martina KLAUSSNER ◽  
Sabine C. WOLF
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Smooth Muscle Cells ◽  
Receptor Antagonist ◽  
Functional Activity ◽  
Protein Concentration ◽  
Map Kinases ◽  
Mitogen Activated Protein ◽  
Eta Receptor ◽  
Eta Receptor Antagonist

Increased endothelin-1 (ET-1) levels are found in patients with atherosclerosis. ET-1 is known to increase the mitotic response of different growth factors already at threshold concentrations. The aim of this study was to investigate the influence of ET-1 on the mitogen-activated protein (MAP) kinases, extracellular signal-regulated protein kinase (ERK) 1 and ERK 2. Smooth muscle cells were incubated with ET-1 at a concentration of 10-7M for 1–120h. ERK 1 and ERK 2 were determined in cell homogenates by electrophoresis. Specific antibodies were used to investigate the amount of ERK 1 or ERK 2 in the homogenate. The functional activity of ERK 1 and ERK 2 was determined. Immunofluorescence microscopy was performed to analyse the translocation of the MAP kinases into the nucleus. ET-1 incubation for 12h decreased ERK 1 concentration by -51%. After 36h of ET-1 application the concentration of ERK 1 increased to control levels again. When the cells were incubated for 120h ERK 1 rose by +65% above control. The incubation with ET-1 in the presence of an ETA receptor antagonist inhibited the increase of ERK 1. ERK 2 showed a comparable time course with an initial decrease in the protein concentration followed by an increase after 120h. Incubation with an ETA receptor antagonist inhibited the increase in protein concentration after 120h. However, the functional activity of both MAP kinases remained unchanged between 1 and 120h. Especially, after 120h of ET-1 incubation no translocation into the nucleus was observed. However, an additional stimulus with angiotensin II resulted in translocation of ERK into the nucleus. These data show that ET-1 increases the protein concentration of MAP kinases ERK 1 and ERK 2 but not their basal activity. Only an additional stimulation with angiotensin II leads to the translocation of ERK into the cell nucleus.

The Apoptotic Effect of Angiotensin II in Human Vascular Smooth Muscle Cells

2000 ◽  
Vol 6 (S2) ◽  
pp. 636-637
Author(s):  
E. Ou ◽  
C. Wei
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Receptor Antagonist ◽  
Vascular Smooth Muscle Cells ◽  
Artery Bypass ◽  
Muscle Cells ◽  
Tunel Staining ◽  
Apoptotic Effect

Angiotensin II is a potent vasoconstrictor and mitogenic factor. However, the effects of angiotensin II on human vascular smooth muscle cells apoptosis remain controversial. Therefore, the current study was designed to investigate the actions of angiotensin II on human vascular smooth muscle cells apoptosis.Human saphenous vein was obtained from coronary artery bypass surgery (n=6) and was minced and incubated in the special tissue culture system in the absence or presence of angiotensin II (10-6 to 10-12M) for 1, 2, 4, 8, 16, & 24 hours. These studies were repeated with losartan (10-6M, AT- 1 receptor antagonist) and PD-123319 (10-6M, AT-2 receptor antagonist). To detect the DNA fragmentation, in situ terminal deoxymucleotidyl transferase dUTP nick end labeling (TUNEL) and DNA agarose gel analyses were performed. An average of 1000 nuclei was analyzed for TUNEL studies.TUNEL staining and DNA gel analysis demonstrated that angiotensin II increased apoptosis in human vascular smooth muscle cells.

Kinin B1 receptor upregulation by angiotensin II and endothelin-1 in rat vascular smooth muscle cells: receptors and mechanisms

2010 ◽  
Vol 299 (5) ◽  
pp. H1625-H1632 ◽  
Author(s):  
Marielle Morand-Contant ◽  
Madhu B. Anand-Srivastava ◽  
Réjean Couture
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Protein Expression ◽  
Smooth Muscle Cells ◽  
Receptor Antagonist ◽  
Vascular Smooth Muscle Cells ◽  
Ang Ii ◽  
Phosphatidylinositol 3 Kinase

Oxidative stress upregulates the kinin B1 receptor (B1R) in diabetes and hypertension. Since angiotensin II (ANG II) and endothelin-1 (ET-1) are increased in these disorders, this study aims at determining the role of these two prooxidative peptides in B1R expression in rat vascular smooth muscle cells (VSMC). In the A10 cell line and aortic VSMC, ANG II enhanced B1R protein expression in a concentration- and time-dependent manner (maximal at 1 μM and 6 h). In A10 cells, ANG II (1 μM) also increased B1R mRNA expression at 3 h and the activation of induced B1R with the agonist [Sar-d-Phe8]-des-Arg9-BK (10 nM, 5 min) significantly enhanced mitogen -activated protein kinase (MAPK1/2) phosphorylation. The enhancing effect of ANG II on B1R protein expression in A10 cells was normalized by the AT1 (losartan) but not by the AT2 (PD123319) receptor antagonist. Furthermore, it was inhibited by inhibitors of phosphatidylinositol 3-kinase (wortmannin) and NF-κB (MG132) but not of MAPK (PD098059). Whereas the ETB receptor antagonist (BQ788) had no effect, the ETA receptor antagonist (BQ123) blocked the effect of ANG II at 6–8 h but not at an early time point. BQ123 and BQ788 also blocked the increasing effect of ET-1 on B1R protein expression. Antioxidants ( N-acetyl-l-cysteine and diphenyleneiodonium) abolished ANG II- and ET-1-increased B1R protein expression. In conclusion, B1R induction is linked to oxidative stress and activation of phosphatidylinositol 3-kinase and NF-κB. The newly synthesized B1R is functional and can activate MAPK signaling in VSMC. The effect of ANG II is mediated by the AT1 receptor and the subsequent activation of ETA through ET-1 release.

Differential ANG II-induced growth activation pathways in mesenteric artery smooth muscle cells from SHR

2001 ◽  
Vol 281 (1) ◽  
pp. H30-H39 ◽  
Author(s):  
Mohammed El Mabrouk ◽  
Rhian M. Touyz ◽  
Ernesto L. Schiffrin
Keyword(s):  
Protein Synthesis ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Dna Synthesis ◽  
Receptor Antagonist ◽  
Kinase Inhibitor ◽  
Muscle Cells ◽  
Vsmc Proliferation

Angiotensin II-induced growth signaling mechanisms were investigated in vascular smooth muscle cells (VSMCs) from mesenteric arteries of sponteneously hypertensive (SHR) and Wistar-Kyoto rats (WKY). In WKY, angiotensin II significantly increased protein synthesis ([3H]leucine incorporation) but not DNA synthesis ([3H]thymidine incorporation). In SHR, angiotensin II increased protein and DNA synthesis. VSMCs from both strains expressed angiotensin type 1 (AT1) and type 2 (AT2) receptors. Losartan (an AT1 receptor antagonist) but not PD-123319 (an AT2 receptor antagonist) attenuated angiotensin II-stimulated protein synthesis in WKY VSMCs. In SHR, losartan and PD-123319 partially inhibited angiotensin II-induced VSMC proliferation. The mitogen-activated protein kinase or extracellular signal-regulated protein kinase (ERK) kinase inhibitor PD-98059 blocked VSMC growth responses to angiotensin II in both strains. Angiotensin II increased ERK1/2 activation more in SHR than WKY, an effect inhibited by losartan but not PD-123319. LY-294002 [a phosphatidylinositol-3 (PI3) kinase inhibitor] blocked angiotensin II-stimulated ERK1/2 activation in SHR but not in WKY, whereas bisindolylmaleimide [a protein kinase C (PKC) inhibitor] was ineffective. In conclusion, angiotensin II stimulates VSMC proliferation via AT1 and AT2 receptors in SHR. In WKY, angiotensin II induces VSMC hypertrophy via AT1receptors. ERK1/2-dependent pathways regulated by intracellular Ca2+ but not PKC mediate these effects. In SHR VSMCs, PI3 kinase plays a role in augmented angiotensin II-induced ERK1/2 phosphorylation. These angiotensin II-mediated signaling events could contribute to vascular remodeling in SHR.

scholarly journals Involvement of MAP kinase activators in angiotensin II-induced activation of MAP kinases in cultured vascular smooth muscle cells

FEBS Letters ◽  
1992 ◽  
Vol 310 (1) ◽  
pp. 41-45 ◽  
Author(s):  
Yoshihiro Ishida ◽  
Yasuhiro Kawahara ◽  
Terutaka Tsuda ◽  
Masanobu Koide ◽  
Mitsuhiro Yokoyama
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Map Kinase ◽  
Vascular Smooth Muscle Cells ◽  
Map Kinases ◽  
Muscle Cells
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