Redox‐sensitive activation of PI3K/Akt pathway in RVLM on endoplasmic reticulum stress‐associated neurogenic hypertension (1095.10)

Abstract

We reported previously that endoplasmic reticulum (ER) stress in the rostral ventrolateral medulla (RVLM), where the sympathetic premotor neurons for maintenance of basal vasomotor tone reside, is engaged in neural mechanism of hypertension. We investigated in the present study the role of the PI3K/Akt signaling in RVLM in the redox‐sensitive and ER stress‐associated neurogenic hypertension. In comparison to normotensive WKY rats, expressions of PI3K and phosphorylated Akt were greater in RVLM of the spontaneously hypertensive rats (SHR), accompanied with increased expressions of ER stress markers, GRP78 and phosphorylated elF2α. Inhibition of PI3K expression in the RVLM of SHR resulted in a significant decrease in mean arterial pressure (MAP), alongside suppressions of the augmented ER stress. However, protect the RVLM from the ER stress with salubrinal had no effect on the augmented PI3K expression or AKT activity, although the MAP was decreased. Treatment of the superoxide dismutase mimetic, tempol, not only abrogated oxidative stress in RVLM, but also blunted the increased expression of PI3K/Akt signaling and ER stress markers, resulting in an decrease in MAP of the SHR. These results suggest that the redox‐sensitive activation of PI3K/Akt pathway in the RVLM may account for the ER stress‐associated neurogenic hypertension in the SHR. Supported by NMRPG8C0261 from National science council in Taiwan.