title: Endoplasmic reticulum stress is involved in cardiac damage and vascular endothelial dysfunction in hypertensive mice.
abstract: OBJECTIVE
  Cardiac damage and vascular dysfunction are major causes of morbidity and mortality in hypertension. In the present study, we explored the beneficial therapeutic effect of endoplasmic reticulum (ER) stress inhibition on cardiac damage and vascular dysfunction in hypertension.
  
  
  RESULTS
  Mice were infused with angiotensin II (400 ng/kg per minute) with or without ER stress inhibitors (taurine-conjugated ursodeoxycholic acid and 4-phenylbutyric acid) for 2 weeks. Mice infused with angiotensin II displayed an increase in blood pressure, cardiac hypertrophy and fibrosis associated with enhanced collagen I content, transforming growth factor-β1 (TGF-β1) activity, and ER stress markers, which were blunted after ER stress inhibition. Hypertension induced ER stress in aorta and mesenteric resistance arteries (MRA), enhanced TGF-β1 activity in aorta but not in MRA, and reduced endothelial NO synthase phosphorylation and endothelium-dependent relaxation (EDR) in aorta and MRA. The inhibition of ER stress significantly reduced TGF-β1 activity, enhanced endothelial NO synthase phosphorylation, and improved EDR. The inhibition of TGF-β1 pathway improved EDR in aorta but not in MRA, whereas the reduction in reactive oxygen species levels ameliorated EDR in MRA only. Infusion of tunicamycin in control mice induced ER stress in aorta and MRA, and reduced EDR by a TGF-β1-dependent mechanism in aorta and reactive oxygen species-dependent mechanism in MRA.
  
  
  CONCLUSIONS
  ER stress inhibition reduces cardiac damage and improves vascular function in hypertension. Therefore, ER stress could be a potential target for cardiovascular diseases.
authors.affiliation: Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University, New Orleans, LA 70112, USA.
authors.forename: Modar
authors.initials: M
authors.lastname: Kassan
authors.forename: Maria
authors.initials: M
authors.lastname: Galán
authors.forename: Megan
authors.initials: M
authors.lastname: Partyka
authors.forename: Zubaida
authors.initials: Z
authors.lastname: Saifudeen
authors.forename: Daniel
authors.initials: D
authors.lastname: Henrion
authors.forename: Mohamed
authors.initials: M
authors.lastname: Trebak
authors.forename: Khalid
authors.initials: K
authors.lastname: Matrougui
mesh_terms: D000818:Animals; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005355:Fibrosis; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology*; D052250:Nitric Oxide Synthase Type III / Q000502:physiology; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000032:analysis; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014655:Vascular Resistance; D014664:Vasodilation
chemical_list: D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse