Nitric oxide synthase II mRNA expression in cardiac tissue of patients with heart failure undergoing cardiac transplantation.
OBJECTIVE
To examine whether inducible nitric oxide synthase is expressed in myocardial tissue of patients with heart failure.


BACKGROUND
There is increasing evidence that alterations in nitric oxide synthesis are of pathophysiologic importance in heart failure. Nitric oxide (NO) can exert negative inotropic and cytotoxic effects on cardiomyocytes. A number of studies have shown altered nitric oxide production by the endothelial constitutive isoform of nitric oxide synthase (NOS III), but there is little information on the role of NOS II. Expression of NOS II could lead to excessive production of NO in the myocardium and affect cardiac contractility.


METHODS
NOS II mRNA expression in myocardial tissue of 18 patients with idiopathic dilated cardiomyopathy (DCM), 7 patients with ischemic cardiopathy and severe ventricular dysfunction (ISCH), 4 patients with acute myocardial infarction (AMI) and 11 controls. Serum concentration of NO2-/NO3- (NOx) was also measured.


RESULTS
NOS II gene expression occurred in all the patients with DCM, in 1 out of the 7 ISCH patients, in 2 out of the 4 patients with AMI and in none of the controls. Moreover, DCM patients showed a significant 6-fold increase in NOx concentration (253+/-47 nm/ml) as compared to controls (40+/-2 nm/ml) P < 0.001, a phenomenon not observed in ISCH patients (56+/-3 nm/ml).


CONCLUSIONS
NOS II expression occurs in failing human cardiac myocytes and can play an specific role in the pathogenesis of DCM.
Orús
J
J
Cardiovascular Institute and Hormonal Laboratory, Hospital Clinic, University of Barcelona, Spain.
Heras
M
M
Morales-Ruiz
M
M
Leivas
A
A
Roig
E
E
Rigol
M
M
Rivera
F
F
Sanz
G
G
Jiménez
W
W
D002311:Cardiomyopathy, Dilated / Q000201:enzymology* / Q000601:surgery*; D005260:Female; D015870:Gene Expression; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II