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

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 (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, 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(2)alpha-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(2)alpha-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. (C) 2004 American Journal of Hypertension, Ltd.