Raf-1 kinase regulates smooth muscle contraction in the rat mesenteric arteries

Kunju Sathishkumar, Uma Yallampalli, Rebekah Elkins, Chandra Yallampalli

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    We investigated the potential role of Raf-1 kinase in mesenteric arterial contraction. Inhibitors of Raf-1 kinase, GW5074, L779450 and ZM 336372 reversed phenylephrine (PE)-induced mesenteric vascular contraction. Studies in vivo in rats showed that GW5074 inhibited PE-induced increase in mean arterial pressure in adult female Sprague-Dawley rats. Isometric tension studies in mesenteric arteries of rats showed that GW5074 did not change the KCl-evoked contraction but significantly inhibited the contractions to PE, 5-HT, U46619, endothelin 1, angiotensin II and phorbol 12, 13-dibutyrate (PDBu). In mesenteric vascular smooth muscle cells (VSMCs), PE stimulated increase in Raf-1 phosphorylation which was inhibited by GW5074. Measurement of [Ca2+]i with Fura-2 showed that GW5074-mediated inhibition of PE-induced contraction was not associated with decreases in [Ca2+]i. VSMCs treated with PE exhibited higher levels of the contractile proteins, p-MYPT1 and p-MLC 20, which was inhibited by GW5074. Similarly, PDBu induced increases in phosphorylation of Raf-1, MLC20 and MYPT1 and this was inhibited by GW5074. However, GW5074 did not have any significant effect on PE/PDBu-induced MEK/ERK activation. The results indicate that Raf-1 kinase plays an important role in the regulation of vascular contractility through regulation of calcium sensitization.

    Original languageEnglish (US)
    Pages (from-to)384-398
    Number of pages15
    JournalJournal of Vascular Research
    Volume47
    Issue number5
    DOIs
    StatePublished - Aug 2010

    Fingerprint

    Proto-Oncogene Proteins c-raf
    Mesenteric Arteries
    Muscle Contraction
    Phenylephrine
    Smooth Muscle
    Phorbol 12,13-Dibutyrate
    Vascular Smooth Muscle
    Smooth Muscle Myocytes
    Blood Vessels
    Phosphorylation
    15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
    Contractile Proteins
    5-iodo-3-((3,5-dibromo-4-hydroxyphenyl)methylene)-2-indolinone
    Fura-2
    Mitogen-Activated Protein Kinase Kinases
    Endothelin-1
    Angiotensin II
    Sprague Dawley Rats
    Serotonin
    Arterial Pressure

    Keywords

    • Agonists
    • Blood pressure
    • Contraction
    • Extracellular signal-regulated kinase
    • Intracellular calcium
    • Mitogen-activated protein kinase
    • Protein kinase C
    • Raf-1
    • Vascular smooth muscle

    ASJC Scopus subject areas

    • Physiology
    • Cardiology and Cardiovascular Medicine

    Cite this

    Raf-1 kinase regulates smooth muscle contraction in the rat mesenteric arteries. / Sathishkumar, Kunju; Yallampalli, Uma; Elkins, Rebekah; Yallampalli, Chandra.

    In: Journal of Vascular Research, Vol. 47, No. 5, 08.2010, p. 384-398.

    Research output: Contribution to journalArticle

    Sathishkumar, K, Yallampalli, U, Elkins, R & Yallampalli, C 2010, 'Raf-1 kinase regulates smooth muscle contraction in the rat mesenteric arteries', Journal of Vascular Research, vol. 47, no. 5, pp. 384-398. https://doi.org/10.1159/000277726
    Sathishkumar, Kunju ; Yallampalli, Uma ; Elkins, Rebekah ; Yallampalli, Chandra. / Raf-1 kinase regulates smooth muscle contraction in the rat mesenteric arteries. In: Journal of Vascular Research. 2010 ; Vol. 47, No. 5. pp. 384-398.
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