title: Role of NADPH oxidase and iNOS in vasoconstrictor responses of vessels from hypertensive and normotensive rats.
abstract: OBJECTIVE
  To analyse the influence of hypertension in the modulation induced by inducible NOS (iNOS)-derived NO and superoxide anion (O(2) (*-)) of vasoconstrictor responses and the sources of O(2) (*-) implicated.
  
  
  METHODS
  Vascular reactivity experiments were performed in segments of aorta from normotensive, Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR); protein and mRNA expressions were respectively measured by western blot and quantitative reverse transcription-polymerase chain reaction and O(2) (*-) production was evaluated by ethidium fluorescence.
  
  
  RESULTS
  The contractile responses to phenylephrine (1 nM-30 microM) and 5-hydroxytryptamine (0.1-100 microM) were greater in aortic segments from SHR than WKY. The selective iNOS inhibitor, 1400W (10 microM), increased the phenylephrine contraction only in WKY segments; however, iNOS protein and mRNA expressions were greater in aorta from SHR than WKY. Superoxide dismutase (SOD, 150 U ml(-1)) reduced phenylephrine and 5-hydroxytryptamine responses only in aorta from SHR; the NAD(P)H oxidase inhibitor apocynin (0.3 mM) decreased phenylephrine and 5-hydroxytryptamine responses more in vessels from SHR than WKY. Co-incubation with SOD plus 1400W potentiated the phenylephrine and 5-hydroxytryptamine responses more in segments from SHR than WKY. O(2) (*-) production was greater in aorta from SHR than WKY; apocynin abolished this difference.
  
  
  CONCLUSIONS
  Increased O(2) (*-) formation from NADP(H) oxidase in vessels from hypertensive rats contributes to the vasoconstrictor responses and counteract the increase of NO from iNOS and the consequent modulation of these responses.
authors.affiliation: Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Y
authors.initials: Y
authors.lastname: Alvarez
authors.forename: A M
authors.initials: AM
authors.lastname: Briones
authors.forename: R
authors.initials: R
authors.lastname: Hernanz
authors.forename: J V
authors.initials: JV
authors.lastname: Pérez-Girón
authors.forename: M J
authors.initials: MJ
authors.lastname: Alonso
authors.forename: M
authors.initials: M
authors.lastname: Salaices
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D005786:Gene Expression Regulation; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010656:Phenylephrine / Q000008:administration & dosage; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology; D018490:Serotonin Agents / Q000008:administration & dosage; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage
chemical_list: D012333:RNA, Messenger; D018490:Serotonin Agents; D014662:Vasoconstrictor Agents; D013481:Superoxides; D010656:Phenylephrine; D009569:Nitric Oxide; D012701:Serotonin; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D019255:NADPH Oxidases