Angiotensin II injures the arterial wall causing increased aortic stiffening in apolipoprotein E-deficient mice

Doris M. Tham, Baby Martin-McNulty, Yi Xin Wang, Valdeci Da Cunha, Dennis W Wilson, Christian N. Athanassious, Andrew F. Powers, Mark E. Sullivan, John C Rutledge

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume283
Issue number6 52-6
StatePublished - Dec 1 2002

Keywords

  • Aneurysm
  • Atherosclerosis
  • Hypertension
  • Vascular stiffness

ASJC Scopus subject areas

  • Physiology

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