title: Angiotensin-(1-7) prevents angiotensin II-induced fibrosis in cremaster microvessels.
abstract: OBJECTIVE
  The effect of the heptapeptide hormone Ang-(1-7) on microvascular fibrosis in rats with Ang II-induced hypertension was investigated, since vascular fibrosis/remodeling plays a prominent role in hypertension-induced end-organ damage and Ang-(1-7) inhibits vascular growth and fibrosis.
  
  
  METHODS
  Fibrosis of cremaster microvessels was studied in male Lewis rats infused with Ang II and/or Ang-(1-7).
  
  
  RESULTS
  Ang II elevated systolic blood pressure by approximately 40 mmHg, while blood pressure was not changed by Ang-(1-7). Ang II increased perivascular fibrosis surrounding 20-50 μm arterioles as well as interstitial fibrosis; coadministration of Ang-(1-7) prevented the increases in fibrosis. The fibrotic factor CTGF and phospho-Smad 2/3, which upregulates CTGF, were increased by Ang II; this effect was prevented by coadministration of Ang-(1-7). Although TGF-β phosphorylates Smad 2/3, TGF-β was no different among treatment groups. In contrast, Ang II increased the MAP kinase phospho-ERK1/2, which also phosphorylates Smad; p-ERK was reduced by Ang-(1-7). Ang-(1-7), in the presence or absence of Ang II, upregulated the MAP kinase phosphatase DUSP1.
  
  
  CONCLUSIONS
  These results suggest that Ang-(1-7) increases DUSP1 to reduce MAP kinase/Smad/CTGF signaling and decrease fibrosis in resistance arterioles, to attenuate end-organ damage associated with chronic hypertension.
authors: Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors: Kyle A
authors: KA
authors: Carver
authors: Thomas L
authors: TL
authors: Smith
authors: Patricia E
authors: PE
authors: Gallagher
authors: E Ann
authors: EA
authors: Tallant
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001160:Arterioles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects*; D002908:Chronic Disease; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; C526316:CCN2 protein, rat; D010446:Peptide Fragments; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D016212:Transforming Growth Factor beta; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D055513:Connective Tissue Growth Factor; D000803:Angiotensin I; D048052:Mitogen-Activated Protein Kinase 3; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; C118790:angiotensin I (1-7)
keywords: DUSP1; MAP kinase; Smad; angiotensin II; angiotensin-(1-7); connective tissue growth factor; fibrosis; microvasculature; microvessels; remodeling