No abstract

Experimental and clinical evidence has been accumulated to indicate that elevated plasma asymmetric dimethylarginine (ADMA) levels can be regarded as a marker of endothelial dysfunction that mediates cardiovascular morbidity by impairing NO-dependent vascular reactions; therefore, it may have a role in the cardiopulmonary adaptation of the neonate. The present study was undertaken to investigate the perinatal NO metabolism by measuring L-arginine, the NO synthase substrate, ADMA, the endogenous inhibitor of NO synthase, and symmetrical dimethylarginine (SDMA), the biologically inactive L-arginine metabolite in umbilical venous and arterial plasma and in peripheral plasma of the neonate. Measurements were done in ten healthy pregnant women at term delivery and in their newborn infants on the second day of life by using liquid chromatography-mass spectrometry method. It was demonstrated that cord blood L-arginine, ADMA, and SDMA levels were markedly elevated with a moderate, but consistent veno-arterial difference suggesting that they are mainly generated by the placental endothelium. L-Arginine and ADMA levels were found to fall significantly (p < 0.001) by the second postnatal day, whereas SDMA remained unaltered. This finding indicates accelerated enzymatic ADMA elimination and reduction in the inhibition of NO-synthase activity. It is concluded that ADMA may play a role in the control of feto-placental circulation and the circulatory adaptation of the neonate.

ADMA level falls after both vaginal and cesarean birth, whereas SDMA level does not. The higher ADMA level after cesarean birth compared with vaginal birth may contribute to decreased nitric oxide production and bioavailability in neonatal vascular beds.

The progressive increase of ADMA levels described by our study among preterm infants suggests that early endothel dysfunction may take part in developmental programming of chronic adult diseases.

The study was undertaken to define the role of aquaporin-2 (AQP2) in renal concentrating performance by measuring urinary AQP2 excretion and urine osmolality in healthy preterm and full-term neonates during early postnatal life. Random urine samples were obtained from 9 full-term newborn infants (mean birth weight 3,218 g, mean gestational age 39.2 weeks) at postnatal ages of 1, 3 and 5 days. Five premature infants with a mean birth weight of 1,570 g and mean gestational age of 30.6 weeks were studied at the end of the 1st week and then weekly up to the 6th week. Urine osmolality (Knauer osmometer), creatinine (modified Jaffé’s method) and AQP2 concentrations (radioimmunoassay) were measured. In full-term neonates, urinary AQP2 excretion showed no consistent changes over the age period studied, while urine osmolality decreased significantly with advancing age. In premature infants, urinary AQP2 excretion remained practically unchanged during the first 4 weeks followed by an abrupt increase thereafter. Urine osmolality did not follow the developmental pattern of AQP2 excretion; its mean values varied only from 78 ± 39 to 174 ± 146 mosm/l during the experimental period. It is concluded that during the early postnatal period, urinary AQP2 excretion does not serve as a direct marker of the renal action of AVP and the renal capacity to concentrate urine.