title: 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.
authors.affiliation: Université de Carthage, Unité de Physiologie Intégrée, Laboratoire de Pathologies Vasculaires, Faculté des Sciences de Bizerte, Tunisia. houcine.dab@fsb.rnu.tn
authors.forename: Houcine
authors.initials: H
authors.lastname: Dab
authors.forename: Rafik
authors.initials: R
authors.lastname: Hachani
authors.forename: Nedra
authors.initials: N
authors.lastname: Dhaouadi
authors.forename: Wassim
authors.initials: W
authors.lastname: Hodroj
authors.forename: Mohsen
authors.initials: M
authors.lastname: Sakly
authors.forename: Jacques
authors.initials: J
authors.lastname: Randon
authors.forename: Giampiero
authors.initials: G
authors.lastname: Bricca
authors.forename: Kamel
authors.initials: K
authors.lastname: Kacem
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D003720:Densitometry; D005263:Femoral Artery / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D005780:Gelatin / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006145:Guanethidine / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D060888:Real-Time Polymerase Chain Reaction; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D000804:Angiotensin II; D005780:Gelatin; D010959:Tissue Plasminogen Activator; D020782:Matrix Metalloproteinases; D019808:Losartan; D009638:Norepinephrine; D006145:Guanethidine