Premium
Involvement of two distinct signalling pathways in IGF ‐1‐mediated central control of hypotensive effects in normotensive and hypertensive rats
Author(s) -
Cheng P.W.,
Kang B.H.,
Lu P.J.,
Lin S.S.,
Ho W.Y.,
Chen H.H.,
Hong L.Z.,
Wu Y.S.,
Hsiao M.,
Tseng C.J.
Publication year - 2014
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12340
Subject(s) - microinjection , ly294002 , mapk/erk pathway , endocrinology , medicine , nitric oxide , kinase , protein kinase b , solitary nucleus , nitric oxide synthase , pi3k/akt/mtor pathway , signal transduction , biology , central nervous system , microbiology and biotechnology
Aims 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 administration 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 ( SHR s). Method Microinjections of the phosphatidylinositol 3‐kinase ( PI 3K) inhibitor LY 294002 and the MAP kinase‐ ERK kinase ( MEK ) inhibitor PD 98059 into the NTS in WKY rats and SHR s were used to study the involvement of IGF ‐1‐induced depressor effects. Result An IGF ‐1 (7.7 pmol) injection into the NTS resulted in a significant decrease in BP and HR in WKY rats and SHR s. 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 SHR s. However, the m RNA and protein expression levels of the IGF ‐1 R showed no significant differences in the NTS of the WKY rats and the SHR s. Conclusion These results suggest that distinct Akt and ERK signalling pathways mediated the IGF ‐1 control of the central depressor effects in WKY rats and SHR s. ERK signalling defects may be associated with the development of hypertension.