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

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 (O 2 −) 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 (ED 50: 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, O 2 −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-F 2α-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 O 2 − and ONOO − production, and plasma free 8-F 2α-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.