Comparative Effect of ACE Inhibition and Angiotensin II Type 1 Receptor Antagonism on Bioavailability of Nitric Oxide in Patients With Coronary Artery Disease Role of Superoxide Dismutase

Background—Flow-dependent, endothelium-mediated vasodilation (FDD) and activity of extracellular superoxide dismutase (EC-SOD), the major antioxidative enzyme of the arterial wall, are severely impaired in patients with coronary artery disease (CAD). We hypothesized that both ACE inhibitor (ACEI) and angiotensin II type 1 receptor antagonist (AT1-A) increase bioavailability of nitric oxide (NO) by reducing oxidative stress in the vessel wall, possibly by increasing EC-SOD activity. Methods and Results—Thirty-five patients with CAD were randomized to 4 weeks of ACEI (ramipril 10 mg/d) or AT1-A (losartan 100 mg/d). FDD of the radial artery was determined by high-resolution ultrasound before and after intra-arterial N-monomethyl-l-arginine (L-NMMA) to inhibit NO synthase and before and after intra-arterial vitamin C to determine the portion of FDD inhibited by oxygen free radicals. EC-SOD activity was determined after release from endothelium by heparin bolus injection. FDD was improved after ramipril and lo...