S-methylisothiourea inhibits inducible nitric oxide synthase and improves left ventricular performance after acute myocardial infarction.
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.
Wildhirt
S M
SM
Department of Cardiac Surgery, Ludwig-Maximilians University, Munich, Germany. wildhirt@hch.med.uni-muen
Suzuki
H
H
Wolf
W P
WP
Dudek
R
R
Horstman
D
D
Weismueller
S
S
Reichart
B
B
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
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D019335:Nitroarginine; D007550:Isothiuronium; D019001:Nitric Oxide Synthase; C027744:S-methylisothiopseudouronium