title: Regression of ventricular and vascular hypertrophy: are there differences between structurally different angiotensin-converting enzyme inhibitors?
abstract: OBJECTIVE
  It is well established that angiotensin-converting enzyme (ACE) inhibitors (ACEI) reduce blood pressure (BP) and hypertrophy of the left ventricle and vessels. The aim of our study was to compare chemically different ACEIs regarding their ability to modulate left ventricular and media hypertrophy, ACE activity and plasma endothelin-1 concentrations in spontaneously hypertensive rats (SHRs).
  
  
  METHODS
  After establishing equi-effective dose regimes, SHRs were treated (3 months) with captopril, enalapril, fosinopril or ramipril (2 x 25, 10, 20 or 1 mg/kg per day or corresponding 1% doses for studying blood pressure-independent effects).
  
  
  RESULTS
  Systolic blood pressure was reduced in SHRs receiving high doses of captopril, enalapril, fosinopril or ramipril (-61, -54, -35 and -47 mmHg), whereas low doses were ineffective. Left ventricular weight was decreased in animals treated with high doses (captopril/enalapril/fosinopril/ramipril: -17/-19/-17/-19%), but not low doses of agents. Media thickness of thoracal aorta was reduced by administering high doses (captopril/enalapril/fosinopril/ramipril: -31/-32/-27/-26%) and low doses (-16/-22/-22/-19%) of agents. ACE activity was reduced in heart, aorta and kidney of rats treated with high and low doses of all ACE inhibitors, whereby high doses showed more pronounced effects. Plasma endothelin-1 concentrations were not altered. A blood-pressure-ineffective treatment with an AT -antagonist revealed similar effects on cardiovascular hypertrophy.
  
  
  CONCLUSIONS
  ACEIs reduce cardiovascular hypertrophy uniformly via an AT -receptor- mediated mechanism, reinforcing the opinion that ACEI effects are indeed class effects. The significance of local renin-angiotensin systems was confirmed by antihypertrophic effects in the aorta that were apparent in the absence of any blood pressure reduction.
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Medical University of Lübeck, Germany. raasch@medinf.mu-luebeck.de
authors.forename: Walter
authors.initials: W
authors.lastname: Raasch
authors.forename: Torsten
authors.initials: T
authors.lastname: Bartels
authors.forename: Christopher
authors.initials: C
authors.lastname: Schwartz
authors.forename: Walter
authors.initials: W
authors.lastname: Häuser
authors.forename: Hartmut
authors.initials: H
authors.lastname: Rütten
authors.forename: Peter
authors.initials: P
authors.lastname: Dominiak
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000473:pathology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage; D002940:Circadian Rhythm / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000008:administration & dosage; D019332:Endothelin-1 / Q000097:blood; D017328:Fosinopril / Q000008:administration & dosage; D017379:Hypertrophy, Left Ventricular / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D017257:Ramipril / Q000008:administration & dosage; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D019332:Endothelin-1; D004656:Enalapril; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D017257:Ramipril; D017328:Fosinopril