title: Treatment of combined aortic regurgitation and systemic hypertension: Insights from an animal model study.
abstract: BACKGROUND
  Hypertension (HT) and aortic valve regurgitation (AR) often coexist but the specific impacts of AR + HT on the left ventricle (LV) are still unknown. The best treatment strategy for this combination of diseases is also unclear. The objectives of this study were 1) to evaluate LV function, remodeling and 2) to assess the effects of the angiotensin-converting enzyme (ACE) inhibitor captopril (C) in rats with AR +/- HT in spontaneously hypertensive rats (SHR).
  
  
  METHODS
  Animals were grouped as follows: normotensive (NT) Wistar-Kyoto, NT + AR, hypertensive SHR (HT), and HT + AR receiving or not captopril (150 mg/kg/d). Hearts were evaluated in vivo by echocardiography and harvested for tissue analysis after 6 months of evolution.
  
  
  RESULTS
  The HT + AR rats had the worst LV hypertrophy (LVH), subendocardial fibrosis, and lowest ejection fraction. Captopril normalized BP in HT and HT + AR, but could not prevent LVH in HT + AR as well as it did in isolated HT. The LV ejection fraction remained below normal in HT + AR + captopril compared to HT alone + captopril. Cardiomyocyte hypertrophy remained in HT + AR + captopril but was normalized in HT + captopril. Subendocardial fibrosis was reduced by captopril in HT + AR.
  
  
  CONCLUSIONS
  The AR + HT rats had the most severe myocardial abnormalities. High dose captopril was effective to slow LVH and preserve normal LV ejection fraction in isolated HT or AR, but was less effective when both pathologies were combined. Prohypertrophic stimuli clearly remain active in HT + AR despite ACE inhibition. These results suggest that a very aggressive medical treatment strategy may be required to optimize LV protection when AR and HT co-exist.
authors.affiliation: Groupe de Recherche en Valvulopathies, Centre de Recherche Hôpital Laval, Institut de cardiologie de Québec, Université Laval, Laval, Québec, Canada. jacques.couet@med.ulaval.ca <jacques.couet@med.ulaval.ca>
authors.forename: Jacques
authors.initials: J
authors.lastname: Couet
authors.forename: Martin
authors.initials: M
authors.lastname: Gaudreau
authors.forename: Dominic
authors.initials: D
authors.lastname: Lachance
authors.forename: Eric
authors.initials: E
authors.lastname: Plante
authors.forename: Elise
authors.initials: E
authors.lastname: Roussel
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Drolet
authors.forename: Marie
authors.initials: M
authors.lastname: Arsenault
mesh_terms: D000818:Animals; D001022:Aortic Valve Insufficiency / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002216:Captopril / Q000627:therapeutic use; D004195:Disease Models, Animal; D004719:Endomyocardial Fibrosis / Q000473:pathology; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006984:Hypertrophy / Q000503:physiopathology; D008297:Male; D009929:Organ Size; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY
chemical_list: D002216:Captopril; D007703:Peptidyl-Dipeptidase A