Premium
Role of MEK and RSK in Blood Pressure Regulation
Author(s) -
Wongk Titus J,
Carmichael Chabrian S,
Nguyen Jenny H,
Andresen Bradley T
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.708.5
Subject(s) - mapk/erk pathway , phosphorylation , mek inhibitor , in vivo , kinase , chemistry , angiotensin ii , extracellular , myosin , microbiology and biotechnology , endocrinology , pharmacology , medicine , blood pressure , biology , biochemistry
A current hypothesis underlying Angiotensin II (Ang II) and norepinephrine (NE) mediated hypertension is that the extracellular regulated kinase cascade (MEK and ERK) is involved in phosphorylation of the regulatory myosin light chain (rMLC). However, the signal transduction is not fully elucidated. We hypothesized that in renal microvascular smooth muscle cells (RμVSMCs) MEK/ERK‐mediated phosphorylation of rMLC is through p90RSK, and this pathway contributes to hypertension. We utilized standard and PhosTag Western blots to measure Ang II and NE‐mediated phosphorylation of ERK, RSK, and rMLC in RμVSMCs. Additionally, CI‐1040 and SL 0101–1, which inhibit MEK and RSK, respectively, were utilized to interrogate this pathway. Simultaneously, an in vivo study was conducted to analyze the anti‐hypertensive effects of the MEK inhibitor CI‐1040 via regular tail cuff measurements. Osmotic minipumps were implanted in mice, delivering 1.0 μg/kg/min Ang II and 5 μg/kg/min NE. Two weeks after insertion of the pumps the mice were gavaged daily with 100 mg/kg of CI‐1040 for an additional 2 weeks. The molecular data suggest that the MEK/ERK/RSK pathway is involved in phosphorylation of rMLC, but contrary to previous studies the preliminary in vivo component failed to show a significant effect of CI‐1040 on blood pressure. TJW and this study were supported by the APS STEP‐UP program.