Physiological regulation of MMPs and tPA/PAI in the arterial wall of rats by noradrenergic tone and angiotensin II
Autor: | Rafik Hachani, Houcine Dab, Kamel Kacem, Giampiero Bricca, Wassim Hodroj, Nedra Dhaouadi, Mohsen Sakly, Jacques Randon |
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Rok vydání: | 2011 |
Předmět: |
Guanethidine
Male Medicine (General) medicine.medical_specialty Vascular smooth muscle Myocytes Smooth Muscle Adrenergic Blood Pressure Stimulation Real-Time Polymerase Chain Reaction Rats Inbred WKY Tissue plasminogen activator Losartan Muscle Smooth Vascular Norepinephrine chemistry.chemical_compound R5-920 Endocrinology Internal medicine Plasminogen Activator Inhibitor 1 Internal Medicine medicine Animals Aorta Abdominal RNA Messenger Angiotensin II Matrix Metalloproteinases Rats Femoral Artery Gene Expression Regulation chemistry Tissue Plasminogen Activator Plasminogen activator inhibitor-1 Gelatin Densitometry medicine.drug |
Zdroj: | Journal of the Renin-Angiotensin-Aldosterone System, Vol 13 (2012) |
ISSN: | 1752-8976 1470-3203 |
Popis: | The interactions between the sympathetic nervous system (SNS) and angiotensin II (ANG II), and their direct effects in vitro on the enzymes involved in vascular extracellular matrix (ECM) degradation, were examined. Rats were treated with guanethidine, losartan or the combined treatments. mRNA, protein and activity of matrix metalloproteinase (MMP)-2 and MMP-9 and mRNA of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) were quantified in abdominal aorta (AA) and femoral artery (FA). Norepinephrine (NE) or ANG II with adrenergic (β, α1 and α2) or losartan antagonists was tested for MMP mRNA response in cultured vascular smooth muscle cells (VSMCs). Combined treatment enhances the inhibition of MMP-2 mRNA and protein level induced by simple treatment in AA. However MMP-9 in AA and MMP mRNA in FA were reduced in the same order by treatments. MMP activities were not affected by treatments. The t-PA/PAI-1 ratio, which reflects the fibrinolytic balance, remained higher after treatments. In cultured VSMCs, NE induced stimulation of MMP mRNA via α2 and β adrenergic receptors and MMP-2 activity via β adrenergic receptors, while ANG II-induced stimulation was abrogated by losartan. Overall, there is a synergic inhibition of both systems on the level of MMP-2 in AA. |
Databáze: | OpenAIRE |
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