title: Comparison of the cardiovascular protection by omapatrilat and lisinopril treatments in DOCA-salt hypertension.
abstract: OBJECTIVE
  To compare the cardiovascular protection provided by omapatrilat and lisinopril in an experimental model of hypertension.
  
  
  METHODS
  Four-week deoxycorticosterone acetate (DOCA)-salt hypertensive (HT) and age-matched normotensive (NT) rats were treated either with omapatrilat (40 mg/kg per day) or lisinopril (20 mg/kg per day) for 2 weeks before sacrifice, and compared with untreated HT and NT rats sacrificed at ages corresponding to either before or after the drug regimens.
  
  
  RESULTS
  Systolic arterial pressure (SAP) of 2 and 4 week HT rats was increased in comparison to age-matched NT rats (P <0.05). Treatment with omapatrilat or lisinopril reduced SAP in HT (P <0.05) similarly by about 10%. Cardiac interstitial collagen, perivascular collagen and media/lumen ratio of coronary arterioles were increased in HT rats. Both treatments partially prevented the rise in perivascular collagen and completely corrected the increased media/lumen ratio in small arterioles from HT (P <0.05). In contrast to NT rats, only a weak coronary dilatation to bradykinin was observed in Langendorff hearts isolated from untreated-HT. This response was slightly improved by lisinopril and markedly improved by omapatrilat (P <0.05). The coronary dilatation to SNP which was reduced in 4-week HT (P <0.05), was partially improved by omapatrilat treatment but not by lisinopril. The enhanced superoxide anion production in aorta from HT rats was partially corrected with omapatrilat and lisinopril. Finally, omapatrilat, unlike lisinopril, markedly reduced mortality in a more severe form of DOCA-salt hypertension.
  
  
  CONCLUSIONS
  Omapatrilat and lisinopril regressed coronary remodelling and cardiac collagen deposition, and reduced vascular oxidative stress in DOCA-salt hypertensive rats. However, despite similar antihypertensive efficacy, omapatrilat was superior to lisinopril in improving the endothelial-dependent coronary dilatation, suggesting a better vascular protection in the DOCA-salt model of hypertension.
authors.affiliation: Faculté de pharmacie, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, Quebec, Canada, H3C 3J7.
authors.forename: Esther
authors.initials: E
authors.lastname: Millette
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Demeilliers
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Laplante
authors.forename: Adil
authors.initials: A
authors.lastname: El Midaoui
authors.forename: Pierre
authors.initials: P
authors.lastname: Moreau
authors.forename: Daniel
authors.initials: D
authors.lastname: Lamontagne
authors.forename: Jacques
authors.initials: J
authors.lastname: de Champlain
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D003094:Collagen / Q000378:metabolism; D003331:Coronary Vessels / Q000503:physiopathology; D003900:Desoxycorticosterone; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D066298:In Vitro Techniques; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride; D013481:Superoxides / Q000378:metabolism; D013841:Thiazepines / Q000627:therapeutic use*; D014666:Vasomotor System / Q000503:physiopathology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D011725:Pyridines; D013841:Thiazepines; D013481:Superoxides; C106266:omapatrilat; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D003094:Collagen; D017706:Lisinopril