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Involvement of Two Distinct Signalling Pathways in IGF‐1‐Mediated Central Control of Hypotensive Effects in Normotensive and Hypertensive Rats
Author(s) -
Tseng ChingJiunn,
Cheng PeiWen
Publication year - 2015
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.29.1_supplement.624.2
Subject(s) - microinjection , ly294002 , mapk/erk pathway , endocrinology , medicine , nitric oxide , kinase , pi3k/akt/mtor pathway , protein kinase b , wortmannin , phosphatidylinositol , signal transduction , biology , microbiology and biotechnology
Insulin‐like growth factor‐1 (IGF‐1) is abundantly expressed in the nucleus tractus solitarii (NTS). In a previous study, we revealed that the induction of nitric oxide (NO) production in the NTS reduces blood pressure (BP). It is well known that both acute and chronic administration of IGF‐I reduce BP. The aim of this study was to evaluate the short‐term hypotensive effect of IGF‐1 in the NTS and to delineate the underlying molecular mechanisms of IGF‐1 in the NTS of normotensive WKY rats and spontaneously hypertensive rats (SHRs). Microinjections of the phosphatidylinositol 3‐kinase (PI3K) inhibitor LY294002 and the MAP kinase‐ERK kinase (MEK) inhibitor PD98059 into the NTS in WKY rats and SHRs were used to study the involvement of IGF‐1‐induced depressor effects. An IGF‐1 (7.7 pmol) injection into the NTS resulted in a significant decrease in BP and HR in WKY rats and SHRs. Immunoblotting and immunohistochemical analysis showed that the microinjection of LY294002 (0.6 pmol) or PD98059 (3.0 pmol) into the NTS attenuated the IGF‐1‐induced depressor effects and Akt or ERK phosphorylation in WKY rats. An attenuation effect of LY294002, but not PD98059, was found in the SHRs. These results suggest that distinct Akt and ERK signalling pathways mediated the IGF‐1 control of the central depressor effects in WKY rats and SHRs. ERK signalling defects may be associated with the development of hypertension.