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Autophagy in RLVM mediates ER stress‐associated neurogenic hypertension in SHR
Author(s) -
Chao YungMei,
Chan Julie Y.H.,
Chan Samuel H.H.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1108.1
Subject(s) - unfolded protein response , autophagy , endoplasmic reticulum , rostral ventrolateral medulla , endocrinology , medicine , microinjection , pathogenesis , chemistry , microbiology and biotechnology , blood pressure , biology , apoptosis , heart rate , biochemistry
Disturbance of endoplasmic reticulum (ER) normal function leads to unfolded protein response known as ER stress which regards as a self‐protective mechanism. We have previously shown that the ER stress in the rostral ventrolateral medulla (RVLM), the location of sympathetic neurons for maintenance of basal vasomotor tone, contributes to the pathogenesis of neurogenic hypertension (NH) in spontaneously hypertensive rats (SHR). However, the underlying mechanism is unknown. Autophagy cleans damaged organelles and proteins in response to stress signaling. Here we verified the linkage between ER stress and autophagy in NH. In addition to ER stress markers, glucose‐regulated protein (GRP78) and the phosphorylated eukaryotic initiation factor 2α (eIF2α), the level of LC3 and LAMP2, two autophagy markers, were significantly higher in SHR than normotensive Wistar‐Kyoto rats. Application of an ER stress protector, salubrinal, in the RVLM of SHR caused a decrease in systolic arterial pressure, alongside suppressions of the ER stress and autophagy. Moreover, microinjection of an autophagy inhibitor, 3‐methyladenie (3‐MA) or siRNA of LC3 into the RVLM of SHR resulted in anti‐hypertension in SHR. Collectively these data suggest that autophagy underlies ER stress‐associated neurogenic hypertension in RVLM of SHR. This study is supported by BMRPG8A0011 to YMC from Kaohsiung Chang Gung Memorial Hospital.