Effects of angiotensin II and angiotensin II type 1 receptor blockade on neointimal formation after stent implantation.
BACKGROUND
To evaluate the effect of supraphysiological levels of angiotensin II and selective angiotensin II type 1 receptor (AT1-receptor) blockade on neointimal formation and systemic endothelial function after stent implantation in the rat abdominal aorta.


METHODS
Male Wistar rats were randomized to one of three groups; control (n=8), angiotensin II infusion (n=9, 200 ng/kg/min), or candesartan cilexetil (n=8,AT1-receptor blocker; rats received 14.4 mg kg(-1) day(-1)). Stents were implanted in the abdominal aorta. Histological analyses were performed at 4 weeks. Endothelial function was determined in isolated thoracic aortic rings.


RESULTS
Neointimal area was increased in the angiotensin II treated group versus the control group, 0.88 mm(2)+/-0.21 versus 0.66 mm(2)+/-0.16 (P<0.05). Neointimal thickness was 171 microm+/-44 in angiotensin II treated animals and 120 microm+/-25 in the control group (P<0.05). In addition, endothelial function was attenuated in angiotensin II treated animals (P=0.01). Candesartan cilexetil treatment did not result in reduction of neointimal area and did not reduce neointimal thickness compared to the control group. Candesartan had no effect on endothelial function.


CONCLUSIONS
Supraphysiological levels of angiotensin II aggravates neointimal formation in the stented rat abdominal aorta, and in parallel decreases endothelial function. AT1-receptor blockade does not reduce neointimal formation in rats without supraphysiological angiotensin II levels.
Groenewegen
Hendrik C
HC
Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, The Netherlands. r.groenewegen@med.umcg.nl
van der Harst
Pim
P
Roks
Anton J M
AJ
Buikema
Hendrik
H
Zijlstra
Felix
F
van Gilst
Wiek H
WH
de Smet
Bart J G L
BJ
D000804:Angiotensin II / Q000097:blood*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D023903:Coronary Restenosis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism* / Q000502:physiology; D015607:Stents / Q000009:adverse effects*; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II