A mechanical stress increases sodium ion content in vascular smooth muscle cells through a calcium-dependent pathway: prevention by cicletanine via a cyclo-oxygenase product

1989 ◽  
Vol 7 ◽  
pp. S322-323 ◽  
Author(s):  
Clelia Rosati ◽  
Sylvie Cavalier ◽  
Pierre Braquet ◽  
Philippe Berthet ◽  
Thierry Tarrade ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Mechanical Stress ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Sodium Ion ◽  
Ion Content ◽  
Calcium Dependent ◽  
Dependent Pathway

Exendin-4 alleviates angiotensin II-induced senescence in vascular smooth muscle cells by inhibiting Rac1 activation via a cAMP/PKA-dependent pathway

2014 ◽  
Vol 307 (12) ◽  
pp. C1130-C1141 ◽  
Author(s):  
Liang Zhao ◽  
Ai Q. Li ◽  
Teng F. Zhou ◽  
Meng Q. Zhang ◽  
Xiao M. Qin
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Therapeutic Potential ◽  
Muscle Cells ◽  
Premature Senescence ◽  
Ang Ii ◽  
Age Related ◽  
Dependent Pathway

Vascular aging has been implicated in the progression of diabetes and age-related cardiovascular disorders. Glucagon-like peptide-1 (GLP-1) is an incretin hormone capable of cytoprotective actions in addition to its glucose-lowering effect. The present study was undertaken to examine whether Exendin-4, a specific ligand for the GLP-1 receptor, could prevent angiotensin (ANG) II-induced premature senescence in vascular smooth muscle cells (VSMCs) and to determine the underlying mechanism involved. Senescence-associated β-galactosidase (SA β-gal) assay showed that ANG II induced premature senescence of VSMCs. Pretreatment with Exendin-4 significantly attenuated ANG II-induced generation of H2O2 and the subsequent VSMC senescence. These effects were, however, reversed in the presence of exendin fragment 9–39, a GLP-1 receptor antagonist, or PKI14-22. Moreover, a marked increase in the levels of p53 and p21 induced by ANG II was blunted by the treatment with Exendin-4. Nevertheless, Exendin-4 failed to decrease ANG II-induced expression of NAD(P)H oxidase 1 (Nox1), NAD(P)H oxidase 4 (Nox4), p22phox, or p47phox in VSMCs. Mechanistically, Exendin-4 blocked ANG II-induced Rac1 activation through the cAMP/PKA signaling cascade. Specifically, NSC23766, a Rac1 inhibitor, abrogated the suppressive effects of Exendin-4 on ANG II-induced premature senescence and H2O2 generation, respectively. Thus Exendin-4 confers resistance to ANG II-induced superoxide anion generation from NAD(P)H oxidase and the resultant VSMC senescence by inhibiting Rac1 activation via a cAMP/PKA-dependent pathway. These findings demonstrate that GLP-1 as well as its analogs (GLP-1-related reagents) may hold therapeutic potential in the treatment of diabetes with cardiovascular disease.

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