title: Angiotensin-(1-7) modulates angiotensin II-induced vasoconstriction in human mammary artery.
abstract: OBJECTIVE
  The renin-angiotensin system plays a key role in cardiovascular pathophysiology and one of its members, angiotensin-(1-7) (ANG-(1-7)), is now recognized as a peptide with the ability to counter-regulate angiotensin II (ANGII) effects. We sought to investigate ANG-(1-7) actions in human vessels, particularly its effect on ANGII-induced vasoconstriction in human mammary arteries (HMA).
  
  
  METHODS
  Samples of HMA from patients submitted to coronary revascularization (22 patients, mean age 67 years) were cut into small rings, mounted in a myograph bath system, normalized and allowed to contract and dilate isometrically. In baseline experiments, the rings were incubated with ANG-(1-7) or vehicle, followed by increasing concentrations of ANGII. This protocol was repeated in the presence of A-779, PD123177, losartan and after mechanical endothelium removal. Western blot analysis and immunofluorescence were also performed in order to verify the presence of Mas receptor in HMA.
  
  
  RESULTS
  ANG-(1-7) significantly attenuated ANGII-induced contraction, producing a maximal inhibition of approximately 65.2%. This effect was not abolished by A-779, PD123177 or endothelium removal. In the presence of losartan, ANGII response was attenuated and no differences were observed between ANG-(1-7) and vehicle treated rings. Finally, we observed, for the first time, that the Mas receptor is expressed in HMA endothelium.
  
  
  CONCLUSIONS
  ANG-(1-7) significantly attenuates ANGII-induced vasoconstriction and, although the Mas receptor is expressed in HMA, this effect seems to be independent of its activation. Additionally, AT2 receptor and endothelium are not involved in this mechanism, which suggests a direct effect on smooth muscle cells.
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.
authors.forename: Luís
authors.initials: L
authors.lastname: Mendonça
authors.forename: Pedro
authors.initials: P
authors.lastname: Mendes-Ferreira
authors.forename: Ana
authors.initials: A
authors.lastname: Bento-Leite
authors.forename: Rui
authors.initials: R
authors.lastname: Cerqueira
authors.forename: Mário Jorge
authors.initials: MJ
authors.lastname: Amorim
authors.forename: Paulo
authors.initials: P
authors.lastname: Pinho
authors.forename: Cármen
authors.initials: C
authors.lastname: Brás-Silva
authors.forename: Adelino F
authors.initials: AF
authors.lastname: Leite-Moreira
authors.forename: Paulo
authors.initials: P
authors.lastname: Castro-Chaves
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000378:metabolism*; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D044139:Receptor, Angiotensin, Type 2; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019808:Losartan