title: S-methylisothiourea inhibits inducible nitric oxide synthase and improves left ventricular performance after acute myocardial infarction.
abstract: The contribution of increased inducible nitric oxide synthase (iNOS) activity to the development of left ventricular dysfunction after acute myocardial infarction (MI) was investigated New Zealand rabbits (n = 24) were randomly treated with either saline, S-methylisothiourea sulfate (SMT; selective iNOS inhibitor) or N-omega-nitro-L-arginine (NOLA; non-isoform selective NOS inhibitor). Left ventricular hemodynamics and myocardial blood flow were measured before coronary occlusion and on postoperative day 3 (POD 3). MI resulted in left ventricular dysfunction and increased myocardial iNOS activity. SMT and NOLA significantly inhibited iNOS activity; SMT, but not NOLA, significantly improved left ventricular maximum +dP/dt and decreased LVEDP; myocardial blood flow in the remote myocardium significantly increased after SMT. Induction of myocardial iNOS after MI on POD 3 contributes to the development of left ventricular dysfunction; modulation of iNOS activity by SMT improves left ventricular performance and may be beneficial after acute MI.
authors.affiliation: Department of Cardiac Surgery, Ludwig-Maximilians University, Munich, Germany. wildhirt@hch.med.uni-muen
authors.forename: S M
authors.initials: SM
authors.lastname: Wildhirt
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: W P
authors.initials: WP
authors.lastname: Wolf
authors.forename: R
authors.initials: R
authors.lastname: Dudek
authors.forename: D
authors.initials: D
authors.lastname: Horstman
authors.forename: S
authors.initials: S
authors.lastname: Weismueller
authors.forename: B
authors.initials: B
authors.lastname: Reichart
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019335:Nitroarginine / Q000494:pharmacology; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D019335:Nitroarginine; D007550:Isothiuronium; D019001:Nitric Oxide Synthase; C027744:S-methylisothiopseudouronium