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.