The Transcription Factor AP1 is Up Regulated through the AT1 Receptor by Activation of SAPK/JNK in the RVLM of Rabbits with Heart Failure

Abstract

Nebraska Medical Center, Omaha, NE, 68198-5850 Angiotensin II (Ang II) plays an important role in the development and progression of chronic heart failure (CHF). This study investigated the Ang II type I receptor (AT1R) in the rostral ventrolateral medulla (RVLM) of rabbits with CHF, its downstream pathway and gene regulation of the transcription factor AP1. The data (Table) show that AT1R mRNA and protein expressions, plasma Ang II, and AP-1 DNA binding activity were significantly higher in CHF than in Sham. The analysis of the SAPK/JNK pathway showed phosphorylated c-Jun proteins, phosphorylated JNK proteins and JNK activity increased significantly in CHF compared to sham. Importantly, intracerebroventricular (ICV) injection of Losartan in CHF rabbits attenuated these increases. These data suggest that central Ang II may activate the AT1R, SAPK/JNK pathway, and up regulate AP1. AP1 may further regulate gene expressions in sympathetic neurons in the CHF state. Supported by NIH grant PO-1 HL 62222