title: L-arginine preferentially dilates stenotic segments of coronary arteries thereby increasing coronary flow.
abstract: OBJECTIVE
  Oxidized LDL cholesterol and cytokines increase arginase and decrease nitric oxide (NO) synthase expression in human endothelial cells, leading to a decrease in NO production. In arteriosclerotic plaques, characterized by increased oxidized LDL and cytokine levels, a sustained local NO reduction might enhance sensitivity of the downstream guanylyl cyclase system towards an acute NO increase. We tested whether application of the NO synthase substrate l-arginine (l-arg, 150 micromol min(-1)) or the NO donor isosorbide dinitrate (ISDN; 0.3 mg) preferentially dilates stenotic coronary artery segments (CS) subsequently increasing poststenotic coronary blood flow (CBF) in patients with coronary artery disease (CAD).
  
  
  METHODS
  Changes in coronary diameter and circumferential surface area were assessed by quantitative coronary angiography (QCA) in a nonstenotic upstream segment, the CS, downstream the CS and in a reference vessel (n = 24). CBF was estimated in a subset of 13 patients by QCA and intracoronary Doppler.
  
  
  RESULTS
  CS ranged from 62% to 89% (77 +/- 5%). l-arg increased minimal luminal diameter of the stenotic segment from 0.98 +/- 0.06 to 1.14 +/- 0.07 mm (P < 0.05) without affecting other coronary segments. Poststenotic CBF increased by 24 +/- 3%. ISDN dilated all segments again with a predominance of CS (25 +/- 4%) and increased poststenotic CBF by 38 +/- 9%. In a multifactorial anova, a medication with an angiotensin-converting enzyme inhibitor (decreasing inflammation and radical formation) and a ratio of LDL/HDL <3.5 were predictive for an l-arg-induced dilation.
  
  
  CONCLUSIONS
  The increase in poststenotic CBF without affecting nondiseased arteries highlights the therapeutic potential of l-arg in patients with CAD.
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Department of Medicine, University Hospital RWTH Aachen, Aachen, Germany. tlauer@ukaachen.de
authors.forename: T
authors.initials: T
authors.lastname: Lauer
authors.forename: P
authors.initials: P
authors.lastname: Kleinbongard
authors.forename: J
authors.initials: J
authors.lastname: Rath
authors.forename: R
authors.initials: R
authors.lastname: Schulz
authors.forename: M
authors.initials: M
authors.lastname: Kelm
authors.forename: T
authors.initials: T
authors.lastname: Rassaf
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001120:Arginine / Q000494:pharmacology / Q000627:therapeutic use*; D001783:Blood Flow Velocity / Q000187:drug effects; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects*; D023921:Coronary Stenosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000494:pharmacology / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D008055:Lipids; D014665:Vasodilator Agents; D001120:Arginine; D007548:Isosorbide Dinitrate