Published Online
on November 15, 2004

A more recent version of this article appeared on January 1, 2005

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Submitted on May 18, 2004
Revised on June 30, 2004

Angiotensin-(1-7) Attenuates Neointimal Formation After Stent Implantation in the Rat

Bas Langeveld^*; Wiek H. van Gilst; René A. Tio; Felix Zijlstra; and Anton J.M. Roks

From the Departments of Clinical Pharmacology (B.L., A.J.M.R, W.H.v.G) and Cardiology (R.A.T., F.Z.), University Hospital Groningen, The Netherlands.

^* To whom correspondence should be addressed. E-mail: be.langeveld{at}med.rug.nl.

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 µg/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 µm; 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.

Key words: angioplasty • angiotensin • aorta • hyperplasia • rats • vasodilation

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