Angiotensin II injures the arterial wall causing increased aortic stiffening in apolipoprotein E-deficient mice.
Cardiovascular diseases, such as atherosclerosis and hypertension, are associated with arterial stiffening. Previous studies showed that ANG II exacerbated atherosclerosis and induced hypertension and aneurysm formation in apolipoprotein E-deficient (apoE-KO) mice. The aim of the present study was to examine the effects of chronic treatment of ANG II on the arterial elastic properties in apoE-KO mice. We hypothesized that ANG II will injure the arterial wall resulting in increased arterial stiffening. Male apoE-KO mice were infused with either ANG II (1.44 mg. kg(-1). day(-1)) or vehicle (PBS) for 30 days. ANG II treatment accelerated atherosclerosis in the carotid artery by sixfold (P < 0.001) and increased blood pressure by 30% (P < 0.05). Additionally, our data demonstrated that ANG II increased arterial stiffening using both in vivo and in vitro methods. ANG II significantly increased pulse wave velocity by 36% (P < 0.01) and decreased arterial elasticity as demonstrated by a more than 900% increase in maximal stiffening (high strain Young's modulus) compared with vehicle (P < 0.05). These functional changes were correlated with morphological and biochemical changes as demonstrated by an increase in collagen content (60%), a decrease in elastin content (74%), and breaks in the internal elastic lamina in the aortic wall. In addition, endothelium-independent vasorelaxation to sodium nitroprusside was impaired in the aortic rings of ANG II-treated mice compared with vehicle. Thus, the present data indicate that ANG II injures the artery wall in multiple ways and arterial stiffening may be a common outcome of ANG II-induced arterial damage.
Tham
Doris M
DM
Department of Internal Medicine, School of Medicine, University of California at Davis, Davis 95616, USA. dmtham@ucdavis.edu
Martin-McNulty
Baby
B
Wang
Yi-Xin
YX
Da Cunha
Valdeci
V
Wilson
Dennis W
DW
Athanassious
Christian N
CN
Powers
Andrew F
AF
Sullivan
Mark E
ME
Rutledge
John C
JC
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000473:pathology*; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced; D001057:Apolipoproteins E / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D001161:Arteriosclerosis / Q000139:chemically induced; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology*; D003094:Collagen / Q000032:analysis; D004334:Drug Administration Schedule; D004548:Elasticity / Q000187:drug effects; D004549:Elastin / Q000032:analysis; D004730:Endothelium, Vascular / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009599:Nitroprusside / Q000494:pharmacology
D001057:Apolipoproteins E; D000804:Angiotensin II; D009599:Nitroprusside; D003094:Collagen; D004549:Elastin; D000109:Acetylcholine