The nitric oxide (NO)/cGMP pathway plays a key role in the regulation of pulmonary vascular tone during the transition from the fetal to the neonatal circulation, and it is impaired in pathophysiological conditions such as pulmonary hypertension. In the present study, we have analyzed the changes in the function and expression of soluble guanylyl cyclase (sGC) in pulmonary arteries during early postnatal maturation in isolated third-branch pulmonary arteries from newborn (3-18 h of age) and 2-wk-old piglets. The expression of sGC beta(1)-subunit in pulmonary arteries increased with postnatal age both at the level of mRNA and protein. The catalytic region of porcine sGC beta(1) was sequenced, showing a 92% homology with the human sequence. This age-dependent increase in sGC expression correlated with increased vasorelaxant responses to the physiological sGC activator NO and to the exogenous sGC activator YC-1, but not to the membrane-permeable cGMP analog 8-bromoguanosine 3',5'-cyclic monophosphate. In conclusion, an increased expression of sGC in pulmonary conduit arteries from 2-wk-old compared with newborn piglets explains, at least partly, the age-dependent increase in the vasorelaxant response of NO and other activators of sGC.
Background: Decreased platelet number and/or function are related to patent ductus arteriosus (PDA) in mice. Whether this is also the case in human infants remains controversial. Objectives: To investigate the association between platelet count nadir within the first 7 days of life and the rate of hemodynamically significant PDA (HSPDA), as well as the rate of response to the treatment with cyclooxygenase (COX) inhibitors. Methods: This is a retrospective study of a cohort of 194 very low-birth-weight (VLBW) infants (<1,500 g) with gestational age <30 weeks. HSPDA was assessed by echocardiography on day 3 of life. Results: HSPDA was present in 105 infants (54.1%). Of these, 101 were treated with COX inhibitors. The treatment failure rate was 21.8%. Median platelet count nadir and rate of thrombocytopenia - defined as platelet count <150 × 109/l and graded as mild (100 to <150 × 109/l), moderate (50 to <100 × 109/l) or severe (<50 × 109/l) - within the first 2 days of life were not significantly associated with the presence of HSPDA on day 3. Moreover, low platelet counts, either on days 1-2 or 3-7, were not significantly associated with the rate of response to treatment with COX inhibitors. Conclusions: Our data provide further evidence for the lack of association between platelet counts within the first days of life and either spontaneous or pharmacological closure of the ductus arteriosus in VLBW infants.
The C242T polymorphism of CYBA (cytochrome B-245 alpha chain), the gene encoding the p22phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, has been linked to several conditions in which oxidative stress plays a pathogenic role. We investigated in a cohort of 451 preterm infants [gestational age (GA) ≤30 weeks] the association of the polymorphism with the risk of developing neonatal respiratory distress syndrome (RDS), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, patent ductus arteriosus, or intraventricular hemorrhage. We observed a significant association of the TT/CT genotype with RDS [odds ratio (OR) 2.34, 95% confidence interval (95% CI) 1.28-3.90], ROP (OR 1.72, 95% CI 1.05-2.80), and BPD (OR 1.60, 95% CI 1.05-2.43). When this dominant model was adjusted to account for GA, birth weight, and sex, it remained significant for the three outcomes. This study is the first to address the association of a polymorphism related to the NADPH family with oxidative stress-related complications of prematurity. Since p22phox is essential for reactive oxygen species production by NADPH oxidase, we hypothesize that genetic variations in the protein may lead to differences in susceptibility to oxidative stress-induced damage in preterm infants. Antioxid. Redox Signal. 27, 1432-1438.
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