title: L-arginine fails to prevent ventricular remodeling and heart failure in the spontaneously hypertensive rat.
abstract: BACKGROUND
  The effects of long-term oral administration of L-arginine, a substrate for nitric oxide (NO) production, on left ventricular (LV) remodeling, myocardial function and the prevention of heart failure (HF) was compared to the angiotensin-converting enzyme (ACE) inhibitor captopril in a rat model of hypertensive HF (aged spontaneously hypertensive rat (SHR)).
  
  
  METHODS
  SHRs and age-matched normotensive Wistar-Kyoto (WKY) rats were assigned to either no treatment, treatment with L-arginine (7.5 g/l in drinking water) or captopril (1 g/l in drinking water) beginning at 14 months of age, a time when SHRs exhibit stable compensated hypertrophy with no hemodynamic impairment; animals were studied at 23 months of age or at the time of HF.
  
  
  RESULTS
  In untreated SHR, relative to WKY, there was significant LV hypertrophy, myocardial fibrosis, and isolated LV muscle performance and response to isoproterenol (ISO) were depressed; and, 7 of 10 SHRs developed HF. Captopril administration to six SHRs attenuated hypertrophy and prevented impaired inotropic responsiveness to ISO, contractile dysfunction, fibrosis, increased passive stiffness, and HF. In contrast, L-arginine administration to SHR increased LV hypertrophy and myocardial fibrosis while cardiac performance was depressed; and 7 of 9 SHRs developed HF. In WKY, L-arginine treatment but not captopril resulted in increased LV weight and the contractile response to ISO was blunted. Neither L-arginine nor captopril treatment of WKY changed fibrosis and HF did not occur.
  
  
  CONCLUSIONS
  These data demonstrate that in contrast to captopril, long-term treatment with L-arginine exacerbates age-related cardiac hypertrophy, fibrosis, and did not prevent contractile dysfunction or the development of HF in aging SHR.
authors.affiliation: Research Service, VA Boston Healthcare System, Boston, Massachusetts, USA. brooksww@bu.edu
authors.forename: Wesley W
authors.initials: WW
authors.lastname: Brooks
authors.forename: Chester H
authors.initials: CH
authors.lastname: Conrad
authors.forename: Kathleen G
authors.initials: KG
authors.lastname: Robinson
authors.forename: Wilson S
authors.initials: WS
authors.lastname: Colucci
authors.forename: Oscar H L
authors.initials: OH
authors.lastname: Bing
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D006332:Cardiomegaly / Q000473:pathology; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000517:prevention & control*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D001120:Arginine; D002216:Captopril