Angiotensin-(1-7) attenuates neointimal formation after stent implantation in the rat.
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.
Langeveld
Bas
B
Department of Clinical Pharmacology, University Hospital Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. be.langeveld@med.rug.nl
van Gilst
Wiek H
WH
Tio
René A
RA
Zijlstra
Felix
F
Roks
Anton J M
AJ
D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery; D001013:Aorta, Thoracic / Q000187:drug effects; D006984:Hypertrophy; D015918:Infusion Pumps, Implantable; D007262:Infusions, Intravenous; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012977:Sodium Nitrite / Q000494:pharmacology; D015607:Stents; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D010446:Peptide Fragments; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D016210:Methacholine Chloride; D010656:Phenylephrine; D000803:Angiotensin I; C118790:angiotensin I (1-7); D012977:Sodium Nitrite