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Silencing of brain p44/42 mitogen‐activated protein kinase ameliorates aldosterone‐induced sympathetic excitation in rats
Author(s) -
Yu Yang,
Zhang ZhiHua,
Wei ShunGuang,
Felder Robert B
Publication year - 2010
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.24.1_supplement.1050.3
Subject(s) - mapk/erk pathway , small interfering rna , aldosterone , protein kinase a , gene silencing , medicine , endocrinology , p38 mitogen activated protein kinases , kinase , chemistry , biology , microbiology and biotechnology , rna , biochemistry , gene
Brain mitogen‐activated protein kinase (MAPK) pathways appear to contribute to aldosterone‐induced sympathetic excitation in rats. We tested whether silencing of brain p44/42 MAPK with small interfering RNAs (siRNAs) would prevent aldosterone‐induced sympathetic excitation in rats. Four days after intracerebroventricular (ICV) injection of SMART pool siRNAs targeting p44/42 MAPK, control siRNA or vehicle, we recorded renal sympathetic nerve activity (RSNA), mean blood pressure (MBP) and heart rate (HR) at baseline and for 4 hours during intravenous infusion of aldosterone. Hypothalamic tissues were then collected for molecular analysis. Treatment with ICV p44/42 siRNA, but not with ICV vehicle or control siRNA, reduced total and phosphorylated p44/42 in the hypothalamus and ameliorated the aldosterone‐induced increases (p<0.05) in RSNA, HR and MBP. The p44/42 siRNA treatment had no effects on hypothalamic p38 MAPK (Western blot). These data strengthen our previous studies showing that brain p44/42 MAPK plays a critical role in mediating renin‐angiotensin‐aldosterone system influences on sympathetic drive. Brain p44/42 MAPK may be a new target for therapeutic intervention in the heart failure syndrome. Supported by a VA Merit Review Award and NIH RO1 HL073986.