title: Prevention of salt induced hypertension and fibrosis by angiotensin converting enzyme inhibitors in Dahl S rats.
abstract: OBJECTIVE
  In Dahl S rats, high salt increases activity of the tissue renin-angiotensin-aldosterone system (RAAS) in the CNS, heart and kidneys. Here, we assessed the effects of chronic angiotensin converting enzyme (ACE) inhibition on salt-induced hypertension and cardiovascular and renal hypertrophy and fibrosis, relative to the extent of ACE blockade.
  
  
  METHODS
  From 4.5 weeks of age, Dahl S rats received either the lipophilic ACE inhibitor trandolapril (1 or 5 mg kg(-1) day(-1)) or the hydrophilic ACE inhibitor lisinopril (10 or 50 mg kg(-1) day(-1)) and a high salt diet was started 0.5 week later. Treatments ended at 9 weeks of age.
  
  
  RESULTS
  High salt diet markedly increased blood pressure (BP), decreased plasma angiotensin II and increased ACE binding densities in brain, heart, aorta and kidneys. Trandolapril and lisinopril prevented 50% of the increase in BP in light and dark period of the day. After the last doses, trandolapril decreased ACE densities by approximately 80% in brain nuclei and heart and lisinopril by approximately 60% in the brain and by approximately 70% in the heart. The two ACE inhibitors prevented right ventricular hypertrophy and attenuated left ventricular hypertrophy but did not affect renal hypertrophy caused by high salt. Both drugs prevented high salt-induced fibrosis in heart, kidney and aorta.
  
  
  CONCLUSIONS
  As the ACE inhibitors could completely prevent tissue fibrosis and partially prevent tissue hypertrophy and hypertension, the tissue RAAS may play a critical role in salt-induced fibrosis, but a lesser role in the hypertrophy.
authors: Hypertension Unit, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors: B
authors: B
authors: Liang
authors: F H H
authors: FH
authors: Leenen
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D004326:Drinking / Q000187:drug effects; D004452:Echocardiography; D005355:Fibrosis; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000517:prevention & control*; D006984:Hypertrophy; D007211:Indoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007279:Injections, Subcutaneous; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D017706:Lisinopril / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012982:Sodium, Dietary / Q000633:toxicity; D013686:Telemetry
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D044140:Receptor, Angiotensin, Type 1; D012982:Sodium, Dietary; C052035:trandolapril; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A