title: Cardiovascular changes in spontaneously hypertensive rats are improved by chronic treatment with zofenopril.
abstract: OBJECTIVE
  The aim of this study was to investigate the effect of chronic treatment with antihypertensive and non-antihypertensive doses of zofenopril on cardiovascular changes in spontaneously hypertensive rats (SHR).
  
  
  METHODS
  Male SHR were treated with 0.5 or 10 mg kg(-1) per day of zofenopril (Z(0.5) and Z(10)) for 3 months. SHR and Wistar-Kyoto rats (WKY) receiving vehicle were used as controls. Systolic blood pressure was measured using the tail cuff method. Left ventricular weight/body weight ratio was calculated as cardiac hypertrophy index. Angiotensin converting enzyme (ACE) activity was determined in plasma and tissues by a fluorimetric method. Vascular reactivity was evaluated on aortic rings by acetylcholine and sodium nitroprusside relaxations. Effects on vascular structure were assessed by lumen diameter, wall thickness and medial cross-sectional area determination. Superoxide anion generation was quantified using lucigenin-amplified chemiluminescence in aorta.
  
  
  RESULTS
  Long-term daily administration of zofenopril (10 mg kg(-1)) to SHR reduced blood pressure to WKY values, decreased cardiac hypertrophy, improved the acetylcholine-induced relaxant response and reversed the vascular remodelling. ACE inhibition and antioxidant activity were involved in these effects. 0.5 mg kg(-1) per day of zofenopril slightly modified blood pressure and the other effects were weaker.
  
  
  CONCLUSIONS
  Antihypertensive effects of chronic treatment with zofenopril were accompanied by recovery of endothelial function and improvement of cardiovascular structure. Low-dose zofenopril had little effect on blood pressure, with some benefits on cardiovascular structure and function. Inhibition of ACE and antioxidant activity were involved in these effects.
authors.affiliation: Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Salamanca, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Gómez-Roso
authors.forename: M J
authors.initials: MJ
authors.lastname: Montero
authors.forename: R
authors.initials: R
authors.lastname: Carrón
authors.forename: M A
authors.initials: MA
authors.lastname: Sevilla
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005470:Fluorometry; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D000975:Antioxidants; C044958:zofenopril; D002216:Captopril