title: ANG II infusion promotes abdominal aortic aneurysms independent of increased blood pressure in hypercholesterolemic mice.
abstract: 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.
authors.affiliation: Rm. 521b, Wethington Bldg., Graduate Center for Nutritional Sciences, Univ. of Kentucky, Lexington, KY 40536-0200, USA. lcassis@uky.edu
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cassis
authors.forename: Manisha
authors.initials: M
authors.lastname: Gupte
authors.forename: Sarah
authors.initials: S
authors.lastname: Thayer
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Richard
authors.initials: R
authors.lastname: Charnigo
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Howatt
authors.forename: Debra L
authors.initials: DL
authors.lastname: Rateri
authors.forename: Alan
authors.initials: A
authors.lastname: Daugherty
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004195:Disease Models, Animal; D006830:Hydralazine / Q000008:administration & dosage; D006937:Hypercholesterolemia / Q000150:complications* / Q000209:etiology / Q000503:physiopathology; D006973:Hypertension / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology / Q000517:prevention & control; D015918:Infusion Pumps, Implantable; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009638:Norepinephrine / Q000008:administration & dosage; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000959:Antihypertensive Agents; D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D011973:Receptors, LDL; D000804:Angiotensin II; D006830:Hydralazine; D009638:Norepinephrine