Inhibition of NOS II prevents cardiac dysfunction in myocardial infarction and congestive heart failure.
Strong expression of the inducible form of nitric oxide synthase (NOS II) has been shown in the myocardium of patients with myocardial infarction (MI). We hypothesized that NOS II plays an important role in the development of MI and subsequent heart failure and that inhibition of NOS II may beneficially alter the course of the disease. Long-term administration (2 mo) of the selective NOS II inhibitor S-methylisothiourea (SMT) to rats with MI significantly improved cardiac function. A significant drop in mortality, lung water content, infarct size, and cardiomyocyte hypertrophy was also associated with the use of SMT. Plasma concentration of nitrite and nitrate was also reduced by SMT. Short-term administration of SMT (first 2 wk only) significantly reduced infarct size; however, it did not improve cardiac dysfunction measured 2 mo after MI. These findings demonstrate that induction of NOS II during MI exerts negative effects on cardiac function and structure. Long-term administration of a selective NOS II inhibitor may prove to be beneficial in the treatment of MI and congestive heart failure.
Saito
Takayuki
T
Department of Pathology, The Montreal General Hospital and McGill University, Montreal, Quebec, Canada H3G 1A4.
Hu
Fu
F
Tayara
Lara
L
Fahas
Linda
L
Shennib
Hani
H
Giaid
Adel
A
D000818:Animals; D015153:Blotting, Western; D003331:Coronary Vessels / Q000502:physiology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000097:blood; D051381:Rats; D011917:Rats, Inbred Lew; D015996:Survival Rate; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D007550:Isothiuronium; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C027744:S-methylisothiopseudouronium