Sensitization of Rats with Low dose of Angiotensin II through Multiple Signaling Pathways in Lamina Terminalis

Abstract

A one wk infusion of a non‐pressor dose of ANGII (induction phase; I) followed by a 1 wk rest (delay period; D) results in a sensitized hypertensive response produced by a subsequent 2 wk infusion of ANGII (expresson period; E). Several brain areas including structures along the lamina terminalis (LT) participate in the regulation of blood pressure. The present study investigated the effects of the non‐pressor sensitizing dose of ANGII (10ng/min/kg) on candidate second messengers in LT that are implicated in sensitization during E. Following a 1 week infusion of either vehicle or ANGII during I LT tissue was collected from rats at the end of D. The dissected tissue was prepared for western blot or for real time PCR.Western blot analyses of LT tissue indicated that phosphorylated cAMP responsive element binding protein (CREB), phosphorylated ERK, and phosphorylated phospholipase C gamma (PLCã) increased 1.5‐, 1.4‐, 1.4 and 1.6 fold respectively (p<0.05). Brain derived neurotrophic factor (BDNF) increased 1.5‐fold. These findings were consistent with real time PCR data showing that BDNF mRNA levels increased 1.6 fold and c‐fos is increased 1.6 fold. These data suggested that the induction by ANGII activates gene expression through PKA, MAPKs and PLC pathways. BDNF may be directly upregulated through the activation of PKA pathway, which further activates TrkB so that AngII‐induced signaling is amplified.