Chronic hypoxia in children with cyanotic congenital heart defects was associated with reduced eNOS activity (0.38 vs 1.06 pmol/mg/min; P<0.0001) compared to acyanotic children.
Observational (n=18)
Does chronic hypoxia alter nitric oxide synthase activity and gene expression in children with congenital heart disease?
Chronic hypoxia in children with cyanotic congenital heart disease downregulates eNOS and upregulates iNOS activity and expression, suggesting a novel adaptive mechanism.
Absolute Event Rate: 0.38% vs 1.06%
p-value: p=<0.0001
BACKGROUND: Chronic hypoxia has been shown to modulate nitric oxide (NO) responses in different cell models, but the relationship between hypoxia and NO synthase (NOS) regulation in humans was not studied. We studied the relationship between endothelial and inducible NOS (eNOS and iNOS) activities and expression and chronic hypoxia in children with cyanotic and acyanotic congenital heart defects. METHODS AND RESULTS: Right atrial tissue was excised from 18 patients during cardiac surgery. eNOS and iNOS activities were measured by conversion of L-H(3)arginine to L-H(3)citrulline. Gene expression of eNOS and iNOS was quantified by competitive reverse transcription-polymerase chain reaction. The eNOS activity and expression were significantly reduced in cyanotic hearts compared with acyanotic hearts: 0.38+/-0.14 versus 1.06+/-0.11 pmol. mg(-1). min(-1) (P<0.0001) and 0.54+/-0.08 versus 0.80+/-0.10 relative optical density (ROD) of cDNA (P<0.0001), respectively. In contrast, iNOS activity and expression were significantly higher in cyanotic than in acyanotic children: 7.04+/-1.20 versus 4.17+/-1.10 pmol. mg(-1). min(-1) (P<0.0001) and 2.55+/-0.11 versus 1.91+/-0.18 ROD of cDNA (P<0.0001), respectively. CONCLUSIONS: Hypoxia downregulates eNOS activity and gene expression in cardiac tissue from patients with cyanotic congenital heart defects. By contrast, iNOS activity and expression are increased in cyanotic children and may represent an alternative mechanism to counteract the effects of hypoxia in the cardiovascular system. Therefore, a novel adaptive mechanism during hypoxia is suggested.
Ferreiro et al. (2001) conducted an observational in Congenital heart disease (n=18). Chronic hypoxia (cyanotic congenital heart defects) vs. Acyanotic congenital heart defects was evaluated on eNOS activity (pmol/mg/min) (p=<0.0001). Chronic hypoxia in children with cyanotic congenital heart defects was associated with reduced eNOS activity (0.38 vs 1.06 pmol/mg/min; P<0.0001) compared to acyanotic children.