Synergistic effect of angiotensin II and nitric oxide synthase inhibitor in increasing aortic stiffness in mice

Richard M. Fitch, John C Rutledge, Yi Xin Wang, Andrew F. Powers, Jih Lie Tseng, Taegan Clary, Gabor M. Rubanyi

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Although they are implicated on their own as risk factors for cardiovascular disease, the potential link between nitric oxide (NO) deficiency, ANG II, and vascular stiffening has not been tested before. We evaluated the role of chronic ANG II treatment and NO deficiency, alone and in combination, on aortic stiffness in mice and tested parameters contributing to increases in active or passive components of vascular stiffness, including blood pressure, vascular smooth muscle contractility, and extracellular matrix components. Untreated (control) mice and mice treated with a NO synthase (NOS) inhibitor [Nω-nitro-L-arginine methyl ester (L-NAME), 0.5 g/l] were implanted with osmotic minipumps delivering ANG II (500 ng·kg -1·min-1) for 28 days. Aortic stiffness was then measured in vivo by pulse wave velocity (PWV) and ex vivo by load-strain analysis to obtain values of maximal passive stiffness (MPS). Blood pressure and aortic contractility ex vivo were measured. ANG II treatment or NOS inhibition with L-NAME did not independently increase vascular stiffness; however, the combined treatments worked synergistically to increase PWV and MPS. The combined treatments of ANG II + L-NAME also significantly increased aortic wall collagen content while decreasing elastin. These novel results suggest that NO deficiency and ANG II act synergistically to increase aortic stiffness in mice predominantly via changes in aortic wall collagen/elastin ratio.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume290
Issue number3
DOIs
StatePublished - Mar 2006

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Vascular Stiffness
Nitric Oxide Synthase
Angiotensin II
NG-Nitroarginine Methyl Ester
Nitric Oxide
Pulse Wave Analysis
Elastin
Collagen
Vascular Smooth Muscle
Extracellular Matrix
Blood Vessels
Arterial Pressure
Cardiovascular Diseases
Blood Pressure

Keywords

  • Blood pressure
  • Collagen
  • Elastin
  • N -nitro-L-arginine methyl ester
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Physiology

Cite this

Synergistic effect of angiotensin II and nitric oxide synthase inhibitor in increasing aortic stiffness in mice. / Fitch, Richard M.; Rutledge, John C; Wang, Yi Xin; Powers, Andrew F.; Tseng, Jih Lie; Clary, Taegan; Rubanyi, Gabor M.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 290, No. 3, 03.2006.

Research output: Contribution to journalArticle

Fitch, Richard M. ; Rutledge, John C ; Wang, Yi Xin ; Powers, Andrew F. ; Tseng, Jih Lie ; Clary, Taegan ; Rubanyi, Gabor M. / Synergistic effect of angiotensin II and nitric oxide synthase inhibitor in increasing aortic stiffness in mice. In: American Journal of Physiology - Heart and Circulatory Physiology. 2006 ; Vol. 290, No. 3.
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