Nitric oxide (NO) directly inhibits OCT1 DNA binding activity in cultured vascular smooth muscle cells (VSMCs).

1996 ◽  
Vol 59 (2) ◽  
pp. 174-174
Author(s):  
X-K. Liu ◽  
D. R. Abernethy ◽  
Y. Li ◽  
O. Shahine ◽  
N. S. Andrawis
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Dna Binding ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Binding Activity ◽  
Dna Binding Activity

Src-Dependent Erk1/2-Mediated Signaling Pathways and Associated Ang Ii-Stimulated Growth Responses Are Altered in Vascular Smooth Muscle Cells from Arteries of Hypertensive Patients.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 721-721
Author(s):  
Rhian M Touyz ◽  
Gang He ◽  
Xiao-Hua Wu ◽  
Jeong Bae Park ◽  
Mohammed El Mabrouk ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Dna Binding ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Vascular Remodeling ◽  
Binding Activity ◽  
Ang Ii ◽  
Hypertensive Patients ◽  
Dna Binding Activity

P154 Molecular mechanisms underlying vascular remodeling in human hypertension are unclear. We investigated c-Src and ERK1/2 activity, proto-oncogene expression, activating protein 1 (AP-1) DNA-binding activity, and DNA and protein synthesis in Ang II-stimulated vascular smooth muscle cells (VSMC) derived from small peripheral arteries from normotensive subjects (NT) (n=5) and age-matched untreated hypertensive patients (HT) (n=10). The media and media:lumen ratio were greater (p<0.05) in arteries from HT than NT, indicating vascular remodeling. Ang II-dose-dependently increased synthesis of DNA and protein, with enhanced effects (p<0.01) in VSMCs from HT. PD98059, a selective inhibitor of the ERK1/2 pathway, attenuated (p<0.01) Ang II-stimulated growth. PD98059 effects were greater in HT than NT. In NT, Ang II transiently increased ERK1/2 phosphorylation. In HT, Ang II-stimulated ERK1/2 activation was significantly augmented (p<0.05 vs NT) and sustained. PP2, a selective Src inhibitor, reduced ERK1/2 activity and normalized responses in HT. Ang II-induced c-Src phosphorylation was 2-3 fold greater in HT than NT. In HT, kinase activation was followed by overexpression of c-fos mRNA and enhanced AP-1 DNA-binding activity. PD98059 attenuated these responses. In HT cells transfected with c-fos antisense oligodeoxynucleotide (ODN), Ang II-stimulated DNA synthesis was reduced compared with sense ODN. These novel findings suggest that vascular remodeling is associated with augmented Ang II-stimulated VSMC growth, which is mediated via hyperactivation of c-Src-regulated, ERK1/2-dependent pathways leading to overexpression of c-fos mRNA and enhanced AP-1 DNA-binding activity. Our data define a signal transduction pathway in VSMCs that could contribute to structural changes and vascular remodeling in essential hypertension.

Thrombin Prevents the Expression of Inducible Nitric Oxide Synthase in Vascular Smooth Muscle Cells by a Proteolytically-Activated Thrombin Receptor

1995 ◽  
Vol 74 (03) ◽  
pp. 980-986 ◽  
Author(s):  
Valérie B Schini-Kerth ◽  
Beate Fißithaler ◽  
Thomas T Andersen ◽  
John W Fenton ◽  
Paul M Vanhoutte ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Inducible Nitric Oxide Synthase ◽  
Muscle Cells ◽  
Thrombin Receptor ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

SummaryProteolytically active forms of thrombin (α- and γ-thrombin) and thrombin receptor peptides inhibited the release of nitrite, a stable endproduct of nitric oxide, evoked by interleukin-1 β(IL-1 β) in cultured vascular smooth muscle cells while proteolytically inactive forms [D-Phe-Pro-Arg chloromethyl ketone-α-thrombin (PPACK-α- thrombin) and diisopropylphosphoryl-α-thrombin (DIP-α-thrombin)] had either no or only minimal inhibitory effects. Under bioassay conditions, perfusates from columns containing IL-1 β-activated vascular smooth muscle cells or cells treated with IL-1βplus PPACK-α-thrombin relaxed detector blood vessels. These relaxations were abolished by the inhibitor of nitric oxide synthesis, NG-nitro-L arginine. No relaxations were obtained with untreated cells or IL-1 β-treated cells in the presence of α-thrombin. The expression of inducible nitric oxide synthase mRNA and protein in vascular smooth muscle cells by IL-1 β was impaired by α-thrombin. These results demonstrate that thrombin regulates the expression of the inducible nitric oxide synthase at a transcriptional level via the proteolytic activation of the thrombin receptor in vascular smooth muscle cells

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