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Differential Effects of Endoplasmic Reticulum Stress on Dipsogenic and Blood Pressure Responses to DOCA‐Salt
Author(s) -
Sigmund Curt,
Jo Fusakazu,
Jo Hiromi,
Hilzendeger Aline,
Cassell Martin,
Rutkowski Thomas,
Davisson Robin,
Grobe Justin
Publication year - 2015
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.29.1_supplement.968.5
Subject(s) - endocrinology , medicine , endoplasmic reticulum , saline , unfolded protein response , chop , chemistry , biochemistry
Endoplasmic reticulum (ER) stress in the subfornical organ has been identified as an important mechanism mediating the hypertensive effects of angiotensin II (Ang‐II). We examined the role of ER stress in the polydipsic and pressor responses to DOCA‐salt. ICV delivery of the ER stress‐reducing chemical chaperone TUDCA had no effect on the magnitude of hypertension, but markedly decreased saline intake to DOCA‐salt. Saline intake increased one day after TUDCA was stopped. Similarly, decreased saline intake was observed after ICV 4‐phenylbutyrate, another chemical chaperone. CCAAT‐enhancer‐binding protein homologous protein (CHOP, a marker of chronic ER stress) immunoreactivity was increased in the SFO of DOCA‐salt mice, but the signal was absent in control and CHOP‐/‐ mice. Electron micrographic studies revealed abnormalities in ER structure (decrease in ER membrane length, distended ER membranes, and decreased ribosome numbers) in the SFO consistent with the induction of ER stress. SFO‐targeted injection of AdGRP78, a molecular chaperone, decreased DOCA‐salt‐induced saline intake. Like the effects of TUDCA, the increase in saline intake in response to DOCA‐salt was blunted in CHOP‐/‐ mice. However, CHOP‐/‐ mice exhibited a similar hypertensive response to DOCA‐salt. These data mechanistically implicate ER stress in saline intake, but not blood pressure responses to DOCA‐salt, and further suggest that CHOP may play a functional role in DOCA‐salt‐induced saline intake. The results suggest a distinction between the importance of ER stress in mediating effects of DOCA‐salt on polydipsia and hypertension.