Brain endoplasmic reticulum stress mechanistically distinguishes the saline-intake and hypertensive response to deoxycorticosterone acetate-salt

Fusakazu Jo; Hiromi Jo; Aline M Hilzendeger; Anthony P Thompson; Martin D Cassell; D Thomas Rutkowski; Robin L Davisson; Justin L Grobe; Curt D Sigmund

doi:10.1161/HYPERTENSIONAHA.115.05377

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Brain endoplasmic reticulum stress mechanistically distinguishes the saline-intake and hypertensive response to deoxycorticosterone acetate-salt

Journal article

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Brain endoplasmic reticulum stress mechanistically distinguishes the saline-intake and hypertensive response to deoxycorticosterone acetate-salt

Fusakazu Jo, Hiromi Jo, Aline M Hilzendeger, Anthony P Thompson, Martin D Cassell, D Thomas Rutkowski, Robin L Davisson, Justin L Grobe and Curt D Sigmund

Hypertension (Dallas, Tex. 1979), Vol.65(6), pp.1341-1348

06/2015

DOI: 10.1161/HYPERTENSIONAHA.115.05377

PMCID: PMC4433403

PMID: 25895586

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Abstract

Endoplasmic reticulum stress has become an important mechanism in hypertension. We examined the role of endoplasmic reticulum stress in mediating the increased saline-intake and hypertensive effects in response to deoxycorticosterone acetate (DOCA)-salt. Intracerebroventricular delivery of the endoplasmic reticulum stress-reducing chemical chaperone tauroursodeoxycholic acid did not affect the magnitude of hypertension, but markedly decreased saline-intake in response to DOCA-salt. Increased saline-intake returned after tauroursodeoxycholic acid was terminated. Decreased saline-intake was also observed after intracerebroventricular infusion of 4-phenylbutyrate, another chemical chaperone. Immunoreactivity to CCAAT homologous binding protein, a marker of irremediable endoplasmic reticulum stress, was increased in the subfornical organ and supraoptic nucleus of DOCA-salt mice, but the signal was absent in control and CCAAT homologous binding protein-deficient mice. Electron microscopy revealed abnormalities in endoplasmic reticulum structure (decrease in membrane length, swollen membranes, and decreased ribosome numbers) in the subfornical organ consistent with endoplasmic reticulum stress. Subfornical organ-targeted adenoviral delivery of GRP78, a resident endoplasmic reticulum chaperone, decreased DOCA-salt-induced saline-intake. The increase in saline-intake in response to DOCA-salt was blunted in CCAAT homologous binding protein-deficient mice, but these mice exhibited a normal hypertensive response. We conclude that (1) brain endoplasmic reticulum stress mediates the saline-intake, but not blood pressure response to DOCA-salt, (2) DOCA-salt causes endoplasmic reticulum stress in the subfornical organ, which when attenuated by GRP78 blunts saline-intake, and (3) CCAAT homologous binding protein may play a functional role in DOCA-salt-induced saline-intake. The results suggest a mechanistic distinction between the importance of endoplasmic reticulum stress in mediating effects of DOCA-salt on saline-intake and blood pressure.

Endoplasmic Reticulum Stress - drug effects

Sodium Chloride - pharmacology

Mice, Inbred C57BL

Reference Values

Random Allocation

Hypertension - physiopathology

Subfornical Organ - drug effects

Brain - metabolism

Animals

Analysis of Variance

Desoxycorticosterone Acetate - pharmacology

Sensitivity and Specificity

Subfornical Organ - physiopathology

Statistics, Nonparametric

Blood Pressure - drug effects

Mice

Infusions, Intraventricular

Sodium Chloride - metabolism

Disease Models, Animal

Endoplasmic Reticulum Stress - physiology

Details

Title: Subtitle: Brain endoplasmic reticulum stress mechanistically distinguishes the saline-intake and hypertensive response to deoxycorticosterone acetate-salt
Creators: Fusakazu Jo - From the Department of Pharmacology (F.J., H.J., A.M.H., J.L.G., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C., D.T.R.), and UIHC Center for Hypertension Research (J.L.G., C.D.S.), Roy J. and Lucille Carver College of Medicine, University of Iowa; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY (R.L.D.); and Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY (R.L.D.)
Hiromi Jo - From the Department of Pharmacology (F.J., H.J., A.M.H., J.L.G., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C., D.T.R.), and UIHC Center for Hypertension Research (J.L.G., C.D.S.), Roy J. and Lucille Carver College of Medicine, University of Iowa; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY (R.L.D.); and Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY (R.L.D.)
Aline M Hilzendeger - From the Department of Pharmacology (F.J., H.J., A.M.H., J.L.G., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C., D.T.R.), and UIHC Center for Hypertension Research (J.L.G., C.D.S.), Roy J. and Lucille Carver College of Medicine, University of Iowa; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY (R.L.D.); and Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY (R.L.D.)
Anthony P Thompson - From the Department of Pharmacology (F.J., H.J., A.M.H., J.L.G., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C., D.T.R.), and UIHC Center for Hypertension Research (J.L.G., C.D.S.), Roy J. and Lucille Carver College of Medicine, University of Iowa; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY (R.L.D.); and Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY (R.L.D.)
Martin D Cassell - From the Department of Pharmacology (F.J., H.J., A.M.H., J.L.G., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C., D.T.R.), and UIHC Center for Hypertension Research (J.L.G., C.D.S.), Roy J. and Lucille Carver College of Medicine, University of Iowa; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY (R.L.D.); and Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY (R.L.D.)
D Thomas Rutkowski - From the Department of Pharmacology (F.J., H.J., A.M.H., J.L.G., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C., D.T.R.), and UIHC Center for Hypertension Research (J.L.G., C.D.S.), Roy J. and Lucille Carver College of Medicine, University of Iowa; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY (R.L.D.); and Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY (R.L.D.)
Robin L Davisson - From the Department of Pharmacology (F.J., H.J., A.M.H., J.L.G., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C., D.T.R.), and UIHC Center for Hypertension Research (J.L.G., C.D.S.), Roy J. and Lucille Carver College of Medicine, University of Iowa; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY (R.L.D.); and Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY (R.L.D.)
Justin L Grobe - From the Department of Pharmacology (F.J., H.J., A.M.H., J.L.G., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C., D.T.R.), and UIHC Center for Hypertension Research (J.L.G., C.D.S.), Roy J. and Lucille Carver College of Medicine, University of Iowa; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY (R.L.D.); and Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY (R.L.D.)
Curt D Sigmund - From the Department of Pharmacology (F.J., H.J., A.M.H., J.L.G., C.D.S.), Department of Anatomy and Cell Biology (A.P.T., M.D.C., D.T.R.), and UIHC Center for Hypertension Research (J.L.G., C.D.S.), Roy J. and Lucille Carver College of Medicine, University of Iowa; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY (R.L.D.); and Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY (R.L.D.). curt-sigmund@uiowa.edu
Resource Type: Journal article
Publication Details: Hypertension (Dallas, Tex. 1979), Vol.65(6), pp.1341-1348
DOI: 10.1161/HYPERTENSIONAHA.115.05377
PMID: 25895586
PMCID: PMC4433403
ISSN: 0194-911X
eISSN: 1524-4563
Grant note: HL084207 / NHLBI NIH HHS R01 HL061446 / NHLBI NIH HHS P01 HL062984 / NHLBI NIH HHS K99/R00 HL098276 / NHLBI NIH HHS R37 HL048058 / NHLBI NIH HHS K99 HL098276 / NHLBI NIH HHS HL048058 / NHLBI NIH HHS R00 HL098276 / NHLBI NIH HHS HL061446 / NHLBI NIH HHS R01 DK084058 / NIDDK NIH HHS P01 HL084207 / NHLBI NIH HHS R01 HL063887 / NHLBI NIH HHS HL063887 / NHLBI NIH HHS
Language: English
Date published: 06/2015
Academic Unit: Molecular Physiology and Biophysics; Anatomy and Cell Biology; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984094552702771

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