Effect of raloxifene and atorvastatin in atherosclerotic process in ovariectomized rats

J Obstet Gynaecol Res. 2013 Jan;39(1):229-36. doi: 10.1111/j.1447-0756.2012.01969.x. Epub 2012 Jul 29.

Abstract

Aim: The goal of this study was to investigate the combined effects of raloxifene and atorvastatin in aged ovariectomized rats during endothelial dysfunction and atherosclerotic process.

Material and methods: This study was conducted on 28 Wistar albino female rats randomly divided into four groups. All groups were ovariectomized and one group was kept as the control group (OVX). For four weeks, the remaining three groups were treated with the statin atorvastatin (OVX+AV), the selective estrogen receptor modulator raloxifene (OVX+RL), and both atorvastatin and raloxifene (OVX+RL+AV), respectively. At the end of the treatment period, all rats were sacrificed and thoracic aortas excised, and endothelial cells were immunohistochemically stained for markers in the atherosclerotic process, such as inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α).

Results: Compared to the ovariectomized group, the iNOS level was significantly increased in the OVX+RL group (P=0.002), but contrarily decreased in the groups OVX+AV (P=0.002) and OVX+RL+AV (P=0.002). eNOS levels in the groups OVX+AV (P=0.002) and OVX+RL+AV (P=0.002) were significantly lower than that in the OVX group. When compared to the OVX group, significant reductions in ET-1 and TNF-α levels were found in all treatment groups. A significant decrement in MCP-1 level was found in the OVX+AV group (P=0.002).

Conclusion: In aged ovariectomized rats, the administration of both raloxifene and atorvastatin significantly decreased the levels of ET-1 and TNF-α on endothelial cells. Combined treatment with these drugs shortly after menopause might play a potential preventive role in the early stages of atherosclerosis development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / metabolism
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / metabolism
  • Atorvastatin
  • Chemokine CCL2 / metabolism
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Estrogen Antagonists / pharmacology
  • Estrogen Antagonists / therapeutic use*
  • Female
  • Heptanoic Acids / pharmacology
  • Heptanoic Acids / therapeutic use*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Nitric Oxide Synthase Type II / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Ovariectomy
  • Pyrroles / pharmacology
  • Pyrroles / therapeutic use*
  • Raloxifene Hydrochloride / pharmacology
  • Raloxifene Hydrochloride / therapeutic use*
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Chemokine CCL2
  • Estrogen Antagonists
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Tumor Necrosis Factor-alpha
  • Raloxifene Hydrochloride
  • Atorvastatin
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III