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Physiological regulation of MMPs and tPA/PAI in the arterial wall of rats by noradrenergic tone and angiotensin II.

Abstract

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.

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  • Publisher Full Text

    • Authors

    Dab H, Hachani R, Dhaouadi N, Hodroj W, Sakly M, Randon J, Bricca G, Kacem K

    Institution

    Université de Carthage, Unité de Physiologie Intégrée, Laboratoire de Pathologies Vasculaires, Faculté des Sciences de Bizerte, Tunisia. houcine.dab@fsb.rnu.tn

    Source

    Journal of the renin-angiotensin-aldosterone system : JRAAS 13:1 2012 Mar pg 36-45

    MeSH

    Angiotensin II
    Animals
    Aorta, Abdominal
    Blood Pressure
    Densitometry
    Femoral Artery
    Gelatin
    Gene Expression Regulation
    Guanethidine
    Losartan
    Male
    Matrix Metalloproteinases
    Muscle, Smooth, Vascular
    Myocytes, Smooth Muscle
    Norepinephrine
    Plasminogen Activator Inhibitor 1
    RNA, Messenger
    Rats
    Rats, Inbred WKY
    Real-Time Polymerase Chain Reaction
    Tissue Plasminogen Activator

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    22071631