Defective phosphatidylinositol 3-kinase signaling in central control of cardiovascular effects in the nucleus tractus solitarii of spontaneously hypertensive rats

Michael Hsiao, Pei Jung Lu, Hsiao Ning Huang, Wan Chen Lo, Wen Yu Ho, Tsung Ching Lai, Hung Ting Chiang, Ching Jiunn Tseng

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Recently we have shown functional involvement of the phosphatidylinositol 3-kinase (P13K)-Akt-nitric oxide synthase (NOS) signaling pathway in central control of cardiovascular effects in the nucleus tractus solitaril (NTS) of normotensive Wistar-Kyoto (WKY) rats. In this study we determined whether P13K/Akt signaling was defective in spontaneously hypertensive rats (SHR). WKY rats and SHR were anesthetized with urethane. Mean blood pressure (MBP) and heart rate (HR) were monitored intra-arterially. Unilateral microinjection (60 nL) of insulin (100 IU/mL) into the NTS produced prominent depressor and bradycardic effects in 8- and 16-week-old normotensive WKY and 8-week-old SHR. However, no significant cardiovascular effects were found in 16-week-old SHR after insulin injection. Furthermore, pretreatment with P13K Inhibitor LY294002 and NOS inhibitor L-NAME into the NTS attenuated the cardiovascular response evoked by insulin in WKY and 8-week-old SHR but not in 16-week-old SHR. Unilateral microinjection of 1 mmol/L of PI(3,4,5)P3 (phosphatidylinositol 3,4,5-triphosphate), a phospholipids second messenger produced by P13K, into the NTS produced prominent depressor and brycardic effects in 8- or 16-week-old WKY rats as well as 8-week-old SHR but not in 16-week-old SHR. Western blot analysis showed no significant increase in Akt phosphorylation in 8-week-old pre-hypertensive SHR after insulin injection. Similar results were also found in hypertensive 16-week-old SHR. Our results indicate that the Akt-independent signaling pathway is involved in NOS activation to regulate cardiovascular effects in the NTS of 8-week-old pre-hypertensive SHR. Both Akt-dependent and Akt-independant signaling pathways are defective in hypertensive 16-week-old SHR.

Original languageEnglish
Pages (from-to)1209-1218
Number of pages10
JournalHypertension Research
Volume31
Issue number6
DOIs
Publication statusPublished - 2008 Jun

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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