Involvement of Rho-kinase and the actin filament network in angiotensin II-induced contraction and extracellular signal-regulated kinase activity in intact rat mesenteric resistance arteries.
We have previously shown that angiotensin II (Ang II) and pressure increase extracellular signal-regulated kinase (ERK) 1/2 activity synergistically in intact, pressurized resistance arteries in vitro. However, the mechanisms by which pressure and Ang II activate ERK1/2 in intact resistance arteries remain to be determined. The purpose of the present study was to investigate the involvement of Rho-kinase and the actin filament network in Ang II- and pressure-induced ERK1/2 activation, as well as in the contractile response induced by Ang II. Mesenteric resistance arteries (200 to 300 microm) were isolated, mounted in an arteriograph, and stimulated by pressure, Ang II, or both. Activation of ERK1/2 was then measured by an in-gel assay. In mesenteric resistance arteries maintained at 70 mm Hg, Ang II (0.1 micromol/L) induced contraction (29+/-1.4% of phenylephrine, 10 micromol/L-induced contraction) and significantly increased ERK1/2 activity. Selective inhibition of Rho-kinase by Y-27632 (10 micromol/L) and selective disruption of the actin filament network by cytochalasin B (10 micromol/L) both decreased the Ang II-induced contraction by 78+/-1.2% and 87+/-1.9%, respectively, and significantly diminished ERK1/2 activity. In the absence of Ang II, increasing intraluminal pressure from 0 to 70 or 120 mm Hg increased ERK1/2 activity. ERK1/2 activity at 120 mm Hg was similar to that observed at 70 mm Hg in the presence of Ang II. Pressure-induced ERK1/2 activation was markedly attenuated by cytochalasin B but not by Y-27632. These results indicate that whereas pressure-induced ERK1/2 activation requires an intact actin filament network, but not Rho-kinase, the activation of ERK1/2 and the contraction induced by Ang II require both Rho-kinase and an intact actin filament network in isolated, intact mesenteric resistance arteries.
Matrougui
K
K
Institut National de la Santé et de la Recherche Médicale (INSERM) U 541, IFR 6, Université Paris VII, Paris, France. matrougui9@hotmail.com
Tankó
L B
LB
Loufrani
L
L
Gorny
D
D
Levy
B I
BI
Tedgui
A
A
Henrion
D
D
D008841:Actin Cytoskeleton / Q000502:physiology*; D000577:Amides / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003571:Cytochalasin B / Q000494:pharmacology; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D054460:rho-Associated Kinases
D000577:Amides; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; D000804:Angiotensin II; C108830:Y 27632; D003571:Cytochalasin B; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases