Angiotensin-(1-7) attenuates neointimal formation after stent implantation in the rat

Hypertension. 2005 Jan;45(1):138-41. doi: 10.1161/01.HYP.0000149382.83973.c2. Epub 2004 Nov 15.

Abstract

Angiotensin-(1-7) is an endogenous, biologically active peptide of the renin-angiotensin system with vasodilatory, antithrombotic, and antiproliferative properties. This study examined the effects of angiotensin-(1-7) infusion on neointimal formation after stent placement in the rat. Male Wistar rats underwent stent implantation in the abdominal aorta or sham surgery. Subsequently, an osmotic minipump was placed for angiotensin-(1-7) (24 microg/kg per hour) or saline administration. After 4 weeks, histomorphometric and histological analyses were performed, and the endothelial function was measured in isolated thoracic aortic rings. Stent implantation resulted in equal mean injury scores within the groups. The angiotensin-(1-7)-treated group displayed a significant reduction in neointimal thickness (112+/-8 versus 141+/-11 microm; P<0.05), neointimal area (0.51+/-0.05 versus 0.70+/-0.07 mm2; P<0.05), and percentage stenosis (10.4+/-1.0 versus 14.0+/-1.3%; P<0.05) compared with the saline-treated group. Furthermore, angiotensin-(1-7) infusion attenuated the stenting-induced impairment in endothelium-dependent relaxation (42.6+/-3.0 versus 64.5+/-6.0% of phenylephrine maximal contraction; P<0.001). In conclusion, angiotensin-(1-7) treatment attenuates neointimal formation after stent implantation in the rat, combined with an improvement of endothelial function.

MeSH terms

  • Angiotensin I / administration & dosage
  • Angiotensin I / pharmacology*
  • Angiotensin I / therapeutic use
  • Animals
  • Aorta, Abdominal / surgery
  • Aorta, Thoracic / drug effects
  • Hypertrophy
  • Infusion Pumps, Implantable
  • Infusions, Intravenous
  • Male
  • Methacholine Chloride / pharmacology
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology*
  • Peptide Fragments / therapeutic use
  • Phenylephrine / pharmacology
  • Rats
  • Rats, Wistar
  • Sodium Nitrite / pharmacology
  • Stents*
  • Tunica Intima / drug effects*
  • Tunica Intima / pathology
  • Vasoconstrictor Agents / pharmacology
  • Vasodilation / drug effects
  • Vasodilator Agents / pharmacology

Substances

  • Peptide Fragments
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Methacholine Chloride
  • Phenylephrine
  • Angiotensin I
  • angiotensin I (1-7)
  • Sodium Nitrite