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The Exaggerated Exercise Pressor Reflex in Heart Failure: MAPK Activation in Peripheral Dorsal Root Ganglia
Author(s) -
Wang Hanjun,
Wang Wei,
Rozanski George J.,
Zucker Irving H.
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.1118.9
Subject(s) - reflex , sensitization , medicine , stimulation , endocrinology , heart failure , mapk/erk pathway , peripheral , p38 mitogen activated protein kinases , anesthesia , chemistry , phosphorylation , immunology , biochemistry
An exaggerated exercise pressor reflex (EPR) causes excessive sympatho‐excitation and exercise intolerance during physical activity in the chronic heart failure (CHF) state. Peripheral sensitization of muscle mechanoreceptors (mechanoreflex) is an important contributor to the exaggerated EPR in CHF whereas the metaboreflex is blunted. The molecular mechanisms underlying the selective sensitization of the mechanoreflex in CHF remain unclear. Here, we proposed that excessive activation of the mitogen‐activated protein kinases (MAPK) pathway in afferent neurons plays a critical role in mediating the sensitized EPR in CHF. Our data demonstrate that phosphorylation of ERK1/2 and p38 but not JNK is increased in lumbar dorsal root ganglia (DRG) of CHF rats compared to sham rats. Furthermore, we found that 1‐ week epidural administration of either the ERK inhibitor PD98059 or the p38 inhibitor SB203580 to lumbar DRGs attenuated the pressor response to either static contraction induced by electrical stimulation of L4/L5 ventral roots or passive stretch (a purely mechanical stimulus) in CHF rats but not in sham rats. Neither treatment improved the blunted cardiovascular responses to hindlimb arterial injection of capsaicin in CHF rats. These data suggest that the increased activation of MAPK pathways in muscle afferent neurons contributes to the genesis of the exaggerated EPR as well as the mechanoreflex in CHF.