Cardiovascular changes in spontaneously hypertensive rats are improved by chronic treatment with zofenopril

Br J Pharmacol. 2009 Dec;158(8):1911-21. doi: 10.1111/j.1476-5381.2009.00491.x.

Abstract

Background and purpose: 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).

Experimental approach: 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 and implications: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacology*
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology
  • Blood Pressure / drug effects*
  • Captopril / administration & dosage
  • Captopril / analogs & derivatives*
  • Captopril / pharmacology
  • Cardiomegaly / etiology
  • Cardiomegaly / prevention & control
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Fluorometry
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Male
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Antioxidants
  • zofenopril
  • Captopril