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Role Of Rostral Ventrolateral Medullary ERK/JNK/p38 MAPK Signaling In The Pressor Effects Of Ethanol And Its Oxidative Product Acetaldehyde In SHRs
Author(s) -
El-Mas Mahmoud M,
Fan Ming,
Abdel-Rahman Abdel A
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.1115.14
Subject(s) - acetaldehyde , dephosphorylation , ethanol , chemistry , rostral ventrolateral medulla , p38 mitogen activated protein kinases , phosphorylation , medicine , endocrinology , mapk/erk pathway , kinase , phosphatase , pharmacology , biochemistry , blood pressure , heart rate
The mitogen‐activated protein kinases (MAPKs) modulate sympathetic activity within the rostral ventrolateral medulla (RVLM). As intra‐RVLM ethanol causes sympathoexcitation and hypertension in SHRs, we tested the hypotheses: (i) altered MAPKs phosphorylation/dephosphorylation in RVLM underlies ethanol hypertension, and (ii) acetaldehyde, oxidative product of ethanol, replicates molecular and related BP effects of ethanol. The BP effect of either drug was evaluated in presence of inhibitors of JNK (SP600125), ERK1/2 (PD98059), p38 (SB203580), or phosphatase (okadaic acid, OKA). Intra‐RVLM ethanol (10 μg) or acetaldehyde (2 μg) caused similar increases in BP. The pressor action is probably mediated via enhanced ERK1/2 activity because it was (i) paralleled with increased RVLM p‐ERK1/2, and (ii) abolished in PD98059‐treated SHRs. SP600125 abrogated ethanol‐but not acetaldehyde‐evoked hypertension, thus implicating JNK in ethanol effects. Despite increased p‐p38, pharmacological intervention revealed no role for p38 in ethanol hypertension. Although phosphatase activity was not altered by either drug, OKA increased baseline BP and abrogated the pressor effect of ethanol or acetaldehyde. Collectively, enhanced ERK1/2 phosphorylation, without any changes in the dephosphorylation profile, accounts for the pressor effect of ethanol or acetaldehyde in SHRs.