title: 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.
abstract: 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 (AT(1)-A) increase bioavailability of nitric oxide (NO) by reducing oxidative stress in the vessel wall, possibly by increasing EC-SOD activity.
  
  
  RESULTS
  Thirty-five patients with CAD were randomized to 4 weeks of ACEI (ramipril 10 mg/d) or AT(1)-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 losartan (each group P<0.01), and in particular, the portion of FDD mediated by NO, ie, inhibited by L-NMMA, was increased by >75% (each group P<0.01). Vitamin C improved FDD initially, an effect that was lost after ramipril or losartan. After therapy, EC-SOD activity was increased by >200% in both groups (ACEI, 14.4+/-1.1 versus 3.8+/-0.9 and AT(1)-A, 13.5+/-1.0 versus 3.9+/-0.9 U. mL(-1). min(-1); each P<0.01). CONCLUSIONS-Four weeks of therapy with ramipril or losartan improves endothelial function to similar extents in patients with CAD by increasing the bioavailability of NO. Our results suggest that beneficial long-term effects of interference with the renin-angiotensin system may be related to reduction of oxidative stress within the arterial wall, mediated in part by increased EC-SOD activity.
authors.affiliation: Abteilung Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany. hornig.burkhard@mh-hannover.de
authors.forename: B
authors.initials: B
authors.lastname: Hornig
authors.forename: U
authors.initials: U
authors.lastname: Landmesser
authors.forename: C
authors.initials: C
authors.lastname: Kohler
authors.forename: D
authors.initials: D
authors.lastname: Ahlersmann
authors.forename: S
authors.initials: S
authors.lastname: Spiekermann
authors.forename: A
authors.initials: A
authors.lastname: Christoph
authors.forename: H
authors.initials: H
authors.lastname: Tatge
authors.forename: H
authors.initials: H
authors.lastname: Drexler
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000627:therapeutic use; D001682:Biological Availability; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D019808:Losartan / Q000627:therapeutic use; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D018384:Oxidative Stress; D017534:Radial Artery / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D017257:Ramipril / Q000627:therapeutic use; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012039:Regional Blood Flow / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014664:Vasodilation; D019323:omega-N-Methylarginine / Q000627:therapeutic use
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D019808:Losartan; D017257:Ramipril; D001205:Ascorbic Acid