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Mitogen‐Activated Protein Kinase Mediates the Effects of Chemokine Stromal Cell‐Derived Factor‐1 (SDF‐1) on Cardiovascular Function and Sympathetic Drive in Rats
Author(s) -
Wei Shun-Guang,
Zhang Zhi-Hua,
Yu Yang,
Felder Robert B.
Publication year - 2012
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.26.1_supplement.891.8
Subject(s) - mapk/erk pathway , medicine , endocrinology , chemokine , protein kinase a , intracellular , signal transduction , mitogen activated protein kinase , sympathetic nervous system , chemistry , kinase , receptor , biology , microbiology and biotechnology , blood pressure
The chemokine SDF‐1 and its receptors are expressed by neurons and glial cells in cardiovascular autonomic regions of the brain. SDF‐1 expression increases in these regions in rats with heart failure (HF). Intracerebroventricular (ICV) administration of SDF‐1 elicits increases in mean blood pressure (MBP, mmHg), heart rate (HR, bpm) and renal sympathetic nerve activity (RSNA) that are exaggerated in rats with HF. SDF‐1 is known to activate mitogen‐activated protein kinase (MAPK) intracellular signaling. We hypothesized that p44/42 MAPK, which has recently been implicated in sympathetic activation in HF, mediates the sympathetic and hemodynamic responses to SDF‐1. In urethane anesthetized adult male rats, ICV injection of SDF‐1 (100 ng) induced significant (p<0.05) increases in MBP (27.6 ± 3.5), HR (55 ± 6) and RSNA (90.1 ± 6.8 %). Pretreatment with ICV PD98059 (1 μg), a selective p44/42 MAPK inhibitor, prevented these SDF‐1 induced responses. ICV minocycline (20 μg), an inhibitor of glial cell activation, significantly (p<0.05) attenuated but did not block the SDF‐1 induced increases in MBP (11.2 ± 2.4), HR (27 ± 4) and RSNA (38.8 ± 4.2 %). These data identify p44/42 MAPK signaling as an obligatory intracellular mechanism mediating the cardiovascular and sympathetic responses to SDF‐1. MAPK signaling in both neurons and glial cells may contribute to these responses. Supported by NIH RO1 HL073986 & HL096671.