Inhibition of oxidative stress and improvement of endothelial function by amlodipine in angiotensin II-infused rats

Ming Sheng Zhou, Edgar A. Jaimes, Leopoldo Raij

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)167-171
Number of pages5
JournalAmerican Journal of Hypertension
Volume17
Issue number2
DOIs
StatePublished - Feb 1 2004

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Amlodipine
Angiotensin II
Oxidative Stress
8-epi-prostaglandin F2alpha
F2-Isoprostanes
Blood Pressure
Hypertrophy
Antihypertensive Agents
Endothelium
Class E Scavenger Receptors
Peroxynitrous Acid
Calcium Channel Blockers
Left Ventricular Hypertrophy
Superoxides
Acetylcholine
Blood Vessels
Sprague Dawley Rats
Antioxidants
Body Weight
Hypertension

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 journalArticle

Zhou, Ming Sheng ; Jaimes, Edgar A. ; Raij, Leopoldo. / Inhibition of oxidative stress and improvement of endothelial function by amlodipine in angiotensin II-infused rats. In: American Journal of Hypertension. 2004 ; Vol. 17, No. 2. pp. 167-171.
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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.

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KW - Amlodipine

KW - Angiotensin

KW - Cardiovascular injury

KW - Endothelial function

KW - Oxidative stress

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