title: Mitochondrial aldehyde dehydrogenase prevents ROS-induced vascular contraction in angiotensin-II hypertensive mice.
abstract: Mitochondrial aldehyde dehydrogenase (ALDH2) is an enzyme that detoxifies aldehydes to carboxylic acids. ALDH2 deficiency is known to increase oxidative stress, which is the imbalance between reactive oxygen species (ROS) generation and antioxidant defense activity. Increased ROS contribute to vascular dysfunction and structural remodeling in hypertension. We hypothesized that ALDH2 plays a protective role to reduce vascular contraction in angiotensin-II (AngII) hypertensive mice. Endothelium-denuded aortic rings from C57BL6 mice, treated with AngII (3.6 μg/kg/min, 14 days), were used to measure isometric force development. Rings treated with daidzin (10 μmol/L), an ALDH2 inhibitor, potentiated contractile responses to phenylephrine (PE) in AngII mice. Tempol (1 mmol/L) and catalase (600 U/mL) attenuated the augmented contractile effect of daidzin. In normotensive mice, contraction to PE in the presence of the daidzin was not different from control, untreated values. AngII aortic rings transfected with ALDH2 recombinant protein decreased contractile responses to PE compared with control. These data suggest that ALDH2 reduces vascular contraction in AngII hypertensive mice. Because tempol and catalase blocked the contractile response of the ALDH2 inhibitor, ROS generation by AngII may be decreased by ALDH2, thereby preventing ROS-induced contraction.
authors: Department of Physiology, Georgia Health Sciences University, Augusta, Georgia 30912-3000, USA. hyehun.choi@gmail.com
authors: Hyehun
authors: H
authors: Choi
authors: Rita C
authors: RC
authors: Tostes
authors: R Clinton
authors: RC
authors: Webb
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D002374:Catalase / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007529:Isoflavones / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000201:enzymology*; D018384:Oxidative Stress / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D007529:Isoflavones; D017382:Reactive Oxygen Species; D013113:Spin Labels; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010656:Phenylephrine; C013908:daidzin; D002374:Catalase; C515029:ALDH2 protein, mouse; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C001803:tempol