Influence of hypoxia on nitric oxide synthase activity and gene expressionin children with congenital heart disease - A novel pathophysiological adaptive mechanism
Cr. Ferreiro et al., Influence of hypoxia on nitric oxide synthase activity and gene expressionin children with congenital heart disease - A novel pathophysiological adaptive mechanism, CIRCULATION, 103(18), 2001, pp. 2272-2276
Citations number
27
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background-Chronic hypoxia has been shown to modulate nitric oxide (NO) res
ponses in different cell models, but the relationship between hypoxia and N
O synthase (NOS) regulation in humans was not studied. We studied the relat
ionship between endothelial and inducible NOS (eNOS and iNOS) activities an
d expression and chronic hypoxia in children with cyanotic and acyanotic co
ngenital 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 q
uantified by competitive reverse transcription-polymerase chain reaction. T
he eNOS activity and expression were significantly reduced in cyanotic hear
ts 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 optic
al density (ROD) of cDNA (P<0.0001), respectively. In contrast, iNOS activi
ty and expression were significantly higher in cyanotic than in acyanotic c
hildren: 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 card
iac tissue from patients with cyanotic congenital heart defects. By contras
t, 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 hyp
oxia is suggested.