title: Temporary treatment with AT1 receptor blocker, valsartan, from early stage of hypertension prevented vascular remodeling.
abstract: BACKGROUND
  The present study examined the inhibitory action of temporary treatment with an angiotensin type 1 (AT(1)) receptor blocker (ARB) on vascular remodeling using hypertensive mice with overexpression of the human renin (hRN) and angiotensinogen (hANG) genes.
  
  
  METHODS
  hRN/hANG transgenic mice (hRN/hANG-Tg) were treated with an ARB, valsartan, from 4 weeks of age. In some mice, valsartan treatment was stopped at 8 weeks of age (temporary treatment). Inflammatory vascular injury was induced by polyethylene-cuff placement around the femoral artery at the age of 10 weeks.
  
  
  RESULTS
  Compared with wild-type (WT) mice, hRN/hANG-Tg showed higher blood pressure (BP) and enhancement of oxidative stress and medial thickening even before cuff placement. Inflammatory vascular remodeling and oxidative stress after cuff placement were further enhanced in hRN/hANG-Tg. Temporary treatment with valsartan continuously lowered BP even after cessation of administration, and inhibited these changes. In contrast, administration of hydralazine lowered BP to a similar level to that with valsartan, but did not inhibit medial thickening and inflammatory vascular remodeling. In contrast to the valsartan treatment, BP immediately increased to the untreated level after cessation of hydralazine.
  
  
  CONCLUSIONS
  These results indicate that temporary ARB treatment leads to prolonged effect of BP lowering and prevents vascular remodeling in hypertensive mice induced by activation of the human renin-angiotensin system. The inhibitory action of valsartan is not due to the BP lowering but is at least in part due to a decrease in oxidative stress and inflammation.
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Inaba
authors.forename: Masaru
authors.initials: M
authors.lastname: Iwai
authors.forename: Megumi
authors.initials: M
authors.lastname: Furuno
authors.forename: Harumi
authors.initials: H
authors.lastname: Kanno
authors.forename: Izumi
authors.initials: I
authors.lastname: Senba
authors.forename: Hideki
authors.initials: H
authors.lastname: Okayama
authors.forename: Masaki
authors.initials: M
authors.lastname: Mogi
authors.forename: Jitsuo
authors.initials: J
authors.lastname: Higaki
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D001158:Arteries / Q000473:pathology; D001808:Blood Vessels / Q000473:pathology*; D004195:Disease Models, Animal; D006830:Hydralazine / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000502:physiology; D058426:Neointima / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D012083:Renin / Q000235:genetics; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D013777:Tetrazoles; D000808:Angiotensinogen; D006830:Hydralazine; D000068756:Valsartan; D019255:NADPH Oxidases; D012083:Renin; D014633:Valine