Abstract
Background: Calcium channel blockers such as amlodipine are effective antihypertensive agents. In this study we investigated the effects of amlodipine on vascular oxidative stress, expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1), and endothelial function in angiotensin (Ang) II-infused rats. Methods: Sprague-Dawley rats were treated with Ang II (0.7 mg/kg/day subcutaneously injected by mini-pump), with or without amlodipine (10 mg/kg/day by gavage), for 5 days and compared with control rats. Levels of aortic ring superoxide (O2-) and peroxynitrite (ONOO-) were determined, and systolic blood pressure (SBP) and endothelium-dependent relaxation were evaluated. Results: Compared with control rats, Ang II-infused rats developed hypertension (175 ± 3 v 135 ± 2 mm Hg, P < .05), aortic hypertrophy (16.9 ± 1.3 v 13.2 ± 0.3 mg/cm, P < .05), left ventricular hypertrophy (0.236 ± 0.003 v 0.204 ± 0.004 g/100 g body weight, P < .05), and impaired endothelium-dependent relaxation (ED50: 6.6 ± 0.2 v 8.0 ± 0.2 -log mol/L acetylcholine concentration, P < .05). Compared with control rats, Ang II-infused rats also had higher aortic levels of LOX-1 mRNA expression, O2-production (1005 ± 140 v 608 ± 159 counts/min/mg, P < .05), ONOO- production (1875 ± 295 v 782 ± 115 counts/min/mg, P < .05), and plasma free 8-F2α-isoprostanes (67.4 ± 19.1 v 27.2 ± 6.1 pg/mL, P < .05). In Ang II-infused rats SBP, aortic hypertrophy, endothelial dysfunction, LOX-1 expression, aortic O2- and ONOO - production, and plasma free 8-F2α-isoprostane levels were significantly reduced by amlodipine treatment. Conclusions: Amlodipine has antihypertensive and antioxidant activity in vivo, which effectively inhibits many of the oxidative stress-dependent mechanisms involved in Ang II-mediated cardiovascular injury.
| Original language | English |
|---|---|
| Pages (from-to) | 167-171 |
| Number of pages | 5 |
| Journal | American Journal of Hypertension |
| Volume | 17 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2004 |
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Keywords
- Amlodipine
- Angiotensin
- Cardiovascular injury
- Endothelial function
- Oxidative stress
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Inhibition of oxidative stress and improvement of endothelial function by amlodipine in angiotensin II-infused rats. / Zhou, Ming Sheng; Jaimes, Edgar A.; Raij, Leopoldo.
In: American Journal of Hypertension, Vol. 17, No. 2, 01.02.2004, p. 167-171.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of oxidative stress and improvement of endothelial function by amlodipine in angiotensin II-infused rats
AU - Zhou, Ming Sheng
AU - Jaimes, Edgar A.
AU - Raij, Leopoldo
PY - 2004/2/1
Y1 - 2004/2/1
N2 - Background: Calcium channel blockers such as amlodipine are effective antihypertensive agents. In this study we investigated the effects of amlodipine on vascular oxidative stress, expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1), and endothelial function in angiotensin (Ang) II-infused rats. Methods: Sprague-Dawley rats were treated with Ang II (0.7 mg/kg/day subcutaneously injected by mini-pump), with or without amlodipine (10 mg/kg/day by gavage), for 5 days and compared with control rats. Levels of aortic ring superoxide (O2-) and peroxynitrite (ONOO-) were determined, and systolic blood pressure (SBP) and endothelium-dependent relaxation were evaluated. Results: Compared with control rats, Ang II-infused rats developed hypertension (175 ± 3 v 135 ± 2 mm Hg, P < .05), aortic hypertrophy (16.9 ± 1.3 v 13.2 ± 0.3 mg/cm, P < .05), left ventricular hypertrophy (0.236 ± 0.003 v 0.204 ± 0.004 g/100 g body weight, P < .05), and impaired endothelium-dependent relaxation (ED50: 6.6 ± 0.2 v 8.0 ± 0.2 -log mol/L acetylcholine concentration, P < .05). Compared with control rats, Ang II-infused rats also had higher aortic levels of LOX-1 mRNA expression, O2-production (1005 ± 140 v 608 ± 159 counts/min/mg, P < .05), ONOO- production (1875 ± 295 v 782 ± 115 counts/min/mg, P < .05), and plasma free 8-F2α-isoprostanes (67.4 ± 19.1 v 27.2 ± 6.1 pg/mL, P < .05). In Ang II-infused rats SBP, aortic hypertrophy, endothelial dysfunction, LOX-1 expression, aortic O2- and ONOO - production, and plasma free 8-F2α-isoprostane levels were significantly reduced by amlodipine treatment. Conclusions: Amlodipine has antihypertensive and antioxidant activity in vivo, which effectively inhibits many of the oxidative stress-dependent mechanisms involved in Ang II-mediated cardiovascular injury.
AB - Background: Calcium channel blockers such as amlodipine are effective antihypertensive agents. In this study we investigated the effects of amlodipine on vascular oxidative stress, expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1), and endothelial function in angiotensin (Ang) II-infused rats. Methods: Sprague-Dawley rats were treated with Ang II (0.7 mg/kg/day subcutaneously injected by mini-pump), with or without amlodipine (10 mg/kg/day by gavage), for 5 days and compared with control rats. Levels of aortic ring superoxide (O2-) and peroxynitrite (ONOO-) were determined, and systolic blood pressure (SBP) and endothelium-dependent relaxation were evaluated. Results: Compared with control rats, Ang II-infused rats developed hypertension (175 ± 3 v 135 ± 2 mm Hg, P < .05), aortic hypertrophy (16.9 ± 1.3 v 13.2 ± 0.3 mg/cm, P < .05), left ventricular hypertrophy (0.236 ± 0.003 v 0.204 ± 0.004 g/100 g body weight, P < .05), and impaired endothelium-dependent relaxation (ED50: 6.6 ± 0.2 v 8.0 ± 0.2 -log mol/L acetylcholine concentration, P < .05). Compared with control rats, Ang II-infused rats also had higher aortic levels of LOX-1 mRNA expression, O2-production (1005 ± 140 v 608 ± 159 counts/min/mg, P < .05), ONOO- production (1875 ± 295 v 782 ± 115 counts/min/mg, P < .05), and plasma free 8-F2α-isoprostanes (67.4 ± 19.1 v 27.2 ± 6.1 pg/mL, P < .05). In Ang II-infused rats SBP, aortic hypertrophy, endothelial dysfunction, LOX-1 expression, aortic O2- and ONOO - production, and plasma free 8-F2α-isoprostane levels were significantly reduced by amlodipine treatment. Conclusions: Amlodipine has antihypertensive and antioxidant activity in vivo, which effectively inhibits many of the oxidative stress-dependent mechanisms involved in Ang II-mediated cardiovascular injury.
KW - Amlodipine
KW - Angiotensin
KW - Cardiovascular injury
KW - Endothelial function
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=1642534463&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1642534463&partnerID=8YFLogxK
U2 - 10.1016/j.amjhyper.2003.09.007
DO - 10.1016/j.amjhyper.2003.09.007
M3 - Article
C2 - 14751660
AN - SCOPUS:1642534463
VL - 17
SP - 167
EP - 171
JO - Journal of clinical hypertension
JF - Journal of clinical hypertension
SN - 0895-7061
IS - 2
ER -