NIH Public Access - Selleck Chemicals

6 downloads 0 Views 1MB Size Report
Key results—Coronary arteriole myogenic tone was significantly reduced under EGFRtk,. GRB2-SOS, JAK, and STAT3 inhibition (53.6±2 vs. 83.4±1.3; 82.8±1; ...
NIH Public Access Author Manuscript Microvasc Res. Author manuscript; available in PMC 2012 January 1.

NIH-PA Author Manuscript

Published in final edited form as: Microvasc Res. 2011 January ; 81(1): 135–142. doi:10.1016/j.mvr.2010.11.001.

Mechanisms of Myogenic Tone of Coronary Arteriole: Role of Down Stream Signaling of the EGFR Tyrosine Kinase Ali H Amin, Zakaria Y Abd Elmageed, Megan Partyka, and Khalid Matrougui Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University, 1430 Tulane Ave, New Orleans LA-70112

Abstract

NIH-PA Author Manuscript

Background and purpose—We previously showed that epidermal growth factor receptor tyrosine kinase (EGFRtk) is essential in the development of myogenic tone. GRB2-SOS, protein kinase B (Akt), Janus kinase (JAK), and Signal Transducer and Activator of Transcription 3 (STAT3) are activated by stretch. Thus, we hypothesized that GRB2-SOS, Akt, JAK and STAT3 are downstream signaling of the EGFR and play role in myogenic tone. Experimental approach—Myogenic tone was determined in freshly isolated coronary arterioles from C57/BL6 mice with and without inhibitors. Pressurized coronary arterioles under 25 and 75 mm Hg were subjected to Western blot analysis to determine signaling phosphorylation. Smooth muscle cells (SMC) stimulated with EGF were used to determine the interaction between signaling. Key results—Coronary arteriole myogenic tone was significantly reduced under EGFRtk, GRB2-SOS, JAK, and STAT3 inhibition (53.6±2 vs. 83.4±1.3; 82.8±1; 83.6±1; 86.1±1 % of passive diameter at 75 mm Hg, p