title: The role of oxidant stress in angiotensin II-mediated contraction of human resistance arteries in the state of health and the presence of cardiovascular disease.
abstract: BACKGROUND
  Angiotensin II is a powerful vasoconstrictor and regulator of cardiovascular growth. Also, it increases formation of reactive oxygen species and contributes to vascular dysfunction. We investigated the role of oxidant stress in contraction of human resistance arteries to angiotensin II, in health and in the presence of cardiovascular disease.
  
  
  METHODS
  Studies of isometric contraction to angiotensin II, using human resistance arteries from healthy volunteers and patients, undergoing cardiac revascularization surgery, were performed by the broad-spectrum antioxidant agent vitamin C and superoxide dismutase mimetic TEMPOL. In the presence of vitamin C, the potency and the maximum contractile response were reduced in both patients and healthy volunteers. Addition of TEMPOL caused a decrease in angiotensin II-induced contraction only in the patients' group.
  
  
  CONCLUSIONS
  Our studies provide evidence for the role of oxidant stress in the contractile response of human resistance arteries to angiotensin II. In patients with cardiovascular disease, the superoxide anion may be the major species involved. In healthy subjects, other reactive oxygen species and the redox-independent vasoconstrictor action of angiotensin II predominate.
  
  
  CONCLUSIONS
  Increased formation of reactive oxygen species, due to angiotensin II, contributes to vascular dysfunction. We determined the oxidative reactivity of human resistance arteries to angiotensin II in healthy subjects and patients, undergoing cardiac revascularization surgery, using the broad-spectrum antioxidant agent, vitamin C, and superoxide dismutase mimetic, TEMPOL. There was a large decrease in potency and maximum of angiotensin II-induced contractile response noted in both groups with the former, while the latter reduced contraction only in the patients' group. Superoxide anion may play a major role in angiotensin II contractions of human resistance arteries in the presence of cardiovascular disease. In healthy subjects, other reactive species and the redox-independent pathways predominate.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, St. George's, University of London, London, SW17 0RE, UK.
authors.forename: Monira B
authors.initials: MB
authors.lastname: Hussain
authors.forename: Valentina O
authors.initials: VO
authors.lastname: Püntmann
authors.forename: Manuel
authors.initials: M
authors.lastname: Mayr
authors.forename: Teck
authors.initials: T
authors.lastname: Khong
authors.forename: Donald R J
authors.initials: DR
authors.lastname: Singer
mesh_terms: D000368:Aged; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000503:physiopathology*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012016:Reference Values; D013113:Spin Labels; D050151:Subcutaneous Fat / Q000098:blood supply; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D017382:Reactive Oxygen Species; D013113:Spin Labels; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D001205:Ascorbic Acid; C001803:tempol