Expression of inducible nitric oxide synthase is increased in patients with heart failure due to ischemic disease.
The objective of the present study was to determine the relationship between nitric oxide synthases (NOS) and heart failure in cardiac tissue from patients with and without cardiac decompensation. Right atrial tissue was excised from patients with coronary artery disease (CAD) and left ventricular ejection fraction (LVEF) <35% (N = 10), and from patients with CAD and LVEF >60% (N = 10) during cardiac surgery. NOS activity was measured by the conversion of L-[H(3)]-arginine to L-[H(3)]-citrulline. Gene expression was quantified by the competitive reverse transcription-polymerase chain reaction. Both endothelial NOS (eNOS) activity and expression were significantly reduced in failing hearts compared to non-failing hearts: 0.36 +/- 0.18 vs 1.51 +/- 0.31 pmol mg-1 min-1 (P < 0.0001) and 0.37 +/- 0.08 vs 0.78 +/- 0.09 relative cDNA absorbance at 320 nm (P < 0.0001), respectively. In contrast, inducible NOS (iNOS) activity and expression were significantly higher in failing hearts than in non-failing hearts: 4.00 +/- 0.90 vs 1.54 +/- 0.65 pmol mg-1 min-1 (P < 0.0001) and 2.19 +/- 0.27 vs 1.43 +/- 0.13 cDNA absorbance at 320 nm (P < 0.0001), respectively. We conclude that heart failure down-regulates both eNOS activity and expression in cardiac tissue from patients with LVEF <35%. In contrast, iNOS activity and expression are increased in failing hearts and may represent an alternative mechanism for nitric oxide production in heart failure due to ischemic disease.
Ferreiro
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Hospital do Coração, Associação do Sanatório Sírio, São Paulo, SP, Brasil.
Chagas
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Carvalho
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Dantas
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Scavone
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Souza
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Buffolo
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da Luz
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D000368:Aged; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000150:complications* / Q000601:surgery; D005260:Female; D015870:Gene Expression; D006333:Heart Failure / Q000201:enzymology* / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D020133:Reverse Transcriptase Polymerase Chain Reaction
C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III