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Activation of MEK1/ERK1/2/iNOS/sGC/PKG pathway contributes to the fall in blood pressure and vascular reactivity in endotoxemic rats
Author(s) -
Korkmaz Belma,
Buharalioglu Kemal,
Demiryurek A. Tuncay,
SahanFirat Seyhan,
Cuez Tuba,
Tunctan Bahar
Publication year - 2009
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.23.1_supplement.932.5
Subject(s) - nitric oxide , chemistry , phosphorylation , protein kinase a , cgmp dependent protein kinase , kinase , pharmacology , medicine , endocrinology , nitric oxide synthase , blood pressure , biochemistry , mitogen activated protein kinase kinase
Increased production of iNOS‐derived NO contributes to fall in blood pressure (BP) and vascular reactivity (VR) during endotoxemia. Inhibition of ERK1/2 activity also reverses the endotoxin (ET)‐induced hypotension via decreased NO production. We investigated whether an increase in protein expression and/or activity of the enzymes involved in MEK1/ERK1/2/iNOS/sGC/PKG pathway contributes to the decrease in BP and VR to norepinephrine (NE) in endotoxemic rats. An inhibitor of ERK1/2 phosphorylation by MEK1/2, U0126, and an inhibitor of iNOS, 1,3‐PBIT, prevented the ET‐induced decrease in BP and VR to NE. sGC inhibitor, ODQ, and PKG inhibitor, KT5823, reversed the decreasing effect of ET on the contractile responses to NE in vitro. ET caused an increase in p‐MEK1, p‐ERK1/2, iNOS and pVASP proteins, and NOx and cGMP levels. U0126 and 1,3‐PBIT did not reverse the ET‐induced increase in p‐MEK1 protein levels. The ET‐induced increase in ERK1/2, iNOS, sGC and PKG protein expressions and activities were prevented by U0126, while 1,3‐PBIT opposed the effect of ET on NOx, p‐VASP protein and cGMP levels. These data demonstrate that activation of MEK1/ERK1/2/iNOS/sGC/PKG pathway contributes to the fall in BP and VR in endotoxemic rats. This study was supported by Mersin Univ (BAP SBE EMB (RBK) 2006‐3 DR) and TUBITAK (SBAG‐3508, 106S299) projects.