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Abnormal calcium homeostasis in the aorta of the spontaneously hypertensive rat is mediated by endoplasmic reticulum stress
Author(s) -
Spitler Kathryn,
Webb R. Clinton
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.1092.1
Subject(s) - tauroursodeoxycholic acid , endoplasmic reticulum , unfolded protein response , homeostasis , endocrinology , medicine , chemistry , aorta , contraction (grammar) , biochemistry
During hypertension, a disruption in calcium (Ca 2+ ) homeostasis contributes to vascular dysfunction. The endoplasmic reticulum (ER) maintains cellular Ca 2+ homeostasis and is easily perturbed leading to ER stress. We hypothesized that enhanced Ca 2+ signaling and contraction in the aorta of the spontaneously hypertensive rat (SHR) is mediated by ER stress. Male Wistar Kyoto and SHR were treated with ER stress inhibitors, tauroursodeoxycholic acid or 4‐phenylbutryic acid (TUDCA and PBA, respectively, 100mg/kg/day, 14 days, i.p.) or vehicle (saline) and the aorta were used for vascular function studies and Western blot analysis. Expression of Ca 2+ regulatory proteins sarco/(ER) Ca 2+ ATPase, calreticulin and calnexin was decreased in the aorta of the TUDCA or PBA treated‐SHR compared to vehicle‐treated SHR. Aortic rings from vehicle‐treated SHR displayed enhanced store‐operated Ca 2+ entry‐induced contraction (6.1 ± 0.4 mN), which was attenuated in SHR treated with either TUDCA (2.2±0.5 mN) or PBA (3.4±0.4 mN). As a measure of ER Ca 2+ storage capacity, caffeine (10 mM) depletion of intracellular Ca 2+ stores measured as a transient contraction was greater in aortic rings from the vehicle‐treated SHR (10.2±1.1 mN) compared to SHR treated with either TUDCA (4.2±0.9 mN ) or PBA (3.9±1.4 mN). These data suggest that ER stress may be a novel therapeutic target for the treatment of hypertension by normalizing Ca 2+ homeostasis.