title: Involvement of two distinct signalling pathways in IGF-1-mediated central control of hypotensive effects in normotensive and hypertensive rats.
abstract: OBJECTIVE
  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 (SHRs).
  
  
  METHODS
  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.
  
  
  RESULTS
  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. However, the mRNA and protein expression levels of the IGF-1R showed no significant differences in the NTS of the WKY rats and the SHRs.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: P-W
authors.initials: PW
authors.lastname: Cheng
authors.forename: B-H
authors.initials: BH
authors.lastname: Kang
authors.forename: P-J
authors.initials: PJ
authors.lastname: Lu
authors.forename: S-S
authors.initials: SS
authors.lastname: Lin
authors.forename: W-Y
authors.initials: WY
authors.lastname: Ho
authors.forename: H-H
authors.initials: HH
authors.lastname: Chen
authors.forename: L-Z
authors.initials: LZ
authors.lastname: Hong
authors.forename: Y-S
authors.initials: YS
authors.lastname: Wu
authors.forename: M
authors.initials: M
authors.lastname: Hsiao
authors.forename: C-J
authors.initials: CJ
authors.lastname: Tseng
mesh_terms: D000818:Animals; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007022:Hypotension / Q000503:physiopathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D051058:Oncogene Protein v-akt / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism
chemical_list: D007334:Insulin-Like Growth Factor I; D051058:Oncogene Protein v-akt
keywords: Akt; ERK; IGF-1; central cardiovascular regulation; nucleus tractus solitarii