TY - JOUR
T1 - ANG II infusion promotes abdominal aortic aneurysms independent of increased blood pressure in hypercholesterolemic mice
AU - Cassis, Lisa A.
AU - Gupte, Manisha
AU - Thayer, Sarah
AU - Zhang, Xuan
AU - Charnigo, Richard
AU - Howatt, Deborah A.
AU - Rateri, Debra L.
AU - Daugherty, Alan
PY - 2009/5
Y1 - 2009/5
N2 - Infusion of ANG II in hyperlipidemic mice augments atherosclerosis and causes formation of abdominal aortic aneurysms (AAAs). The purpose of this study was to define the contribution of ANG II-induced hypertension to these vascular pathologies. Male apolipoprotein E (apoE)- and LDL receptor (LDLr)-deficient mice were infused with ANG II (1,000 ng·kg-1·min -1) or norepinephrine (NE; 5.6 mg·kg -1·day-1) for 28 days. Infusion of ANG II or NE increased mean arterial pressure (MAP; ANG II, 133 ± 2.8; NE, 129 ± 13 mmHg) to a similar extent compared with baseline blood pressures (MAP, 107 ± 2 mmHg). Abdominal aortic width increased in both apoE-deficient (apoE-/-) or LDLr-deficient (LDLr-/-) mice infused with ANG II (apoE-/-: 1.4 ± 0.1; LDLr-/-: 1.6 ± 0.2 mm). In contrast, NE did not change diameters of abdominal aortas (apoE-/-: 0.91 ± 0.03; LDLr-/-: 0.87 ± 0.02 mm). Similarly, atherosclerotic lesions in aortic arches were much greater in mice infused with ANG II compared with NE. At a subpressor infusion rate of ANG II (500 ng·kg-1·min-1), AAAs developed in 50% of apoE-/- mice. Alternatively, administration of hydralazine (250 mg/l) to ANG II-infused apoE-/- mice (1,000 ng·kg-1·min-1) lowered systolic blood pressure (day 28: ANG II, 157 ± 6; ANG II/hydralazine, 135 ± 6 mmHg) but did not prevent AAA formation or atherosclerosis. These results demonstrate that infusion of ANG II to hyperlipidemic mice induces AAAs and augments atherosclerosis independent of increased blood pressure.
AB - Infusion of ANG II in hyperlipidemic mice augments atherosclerosis and causes formation of abdominal aortic aneurysms (AAAs). The purpose of this study was to define the contribution of ANG II-induced hypertension to these vascular pathologies. Male apolipoprotein E (apoE)- and LDL receptor (LDLr)-deficient mice were infused with ANG II (1,000 ng·kg-1·min -1) or norepinephrine (NE; 5.6 mg·kg -1·day-1) for 28 days. Infusion of ANG II or NE increased mean arterial pressure (MAP; ANG II, 133 ± 2.8; NE, 129 ± 13 mmHg) to a similar extent compared with baseline blood pressures (MAP, 107 ± 2 mmHg). Abdominal aortic width increased in both apoE-deficient (apoE-/-) or LDLr-deficient (LDLr-/-) mice infused with ANG II (apoE-/-: 1.4 ± 0.1; LDLr-/-: 1.6 ± 0.2 mm). In contrast, NE did not change diameters of abdominal aortas (apoE-/-: 0.91 ± 0.03; LDLr-/-: 0.87 ± 0.02 mm). Similarly, atherosclerotic lesions in aortic arches were much greater in mice infused with ANG II compared with NE. At a subpressor infusion rate of ANG II (500 ng·kg-1·min-1), AAAs developed in 50% of apoE-/- mice. Alternatively, administration of hydralazine (250 mg/l) to ANG II-infused apoE-/- mice (1,000 ng·kg-1·min-1) lowered systolic blood pressure (day 28: ANG II, 157 ± 6; ANG II/hydralazine, 135 ± 6 mmHg) but did not prevent AAA formation or atherosclerosis. These results demonstrate that infusion of ANG II to hyperlipidemic mice induces AAAs and augments atherosclerosis independent of increased blood pressure.
KW - Aneurysms
KW - Hypertension
KW - Vascular lesions
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U2 - 10.1152/ajpheart.00028.2009
DO - 10.1152/ajpheart.00028.2009
M3 - Article
C2 - 19252100
AN - SCOPUS:66149124383
SN - 0363-6135
VL - 296
SP - H1660-H1665
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 5
ER -