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 language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 290 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2006 |
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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 journal › Article
}
TY - JOUR
T1 - Synergistic effect of angiotensin II and nitric oxide synthase inhibitor in increasing aortic stiffness in mice
AU - Fitch, Richard M.
AU - Rutledge, John C
AU - Wang, Yi Xin
AU - Powers, Andrew F.
AU - Tseng, Jih Lie
AU - Clary, Taegan
AU - Rubanyi, Gabor M.
PY - 2006/3
Y1 - 2006/3
N2 - 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.
AB - 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.
KW - Blood pressure
KW - Collagen
KW - Elastin
KW - N -nitro-L-arginine methyl ester
KW - Vascular smooth muscle
UR - http://www.scopus.com/inward/record.url?scp=33645728559&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645728559&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00327.2005
DO - 10.1152/ajpheart.00327.2005
M3 - Article
C2 - 16272204
AN - SCOPUS:33645728559
VL - 290
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 3
ER -