Nitric Oxide and Endothelin 1 during Postnatal Life

Abstract

Nitric oxide (NO) is a potent vasodilator produced by endothelial cells. Endothelin 1 (ET-1), another agent made by endothelial cells, is the most potent vasoconstrictor known to date. Endogenous NO and ET-1 may play a part in the normal physiological pulmonary vascular changes during the postnatal period. However, the changes of NO and ET-1 in healthy neonates have not been defined. We determined serum NO metabolites, i.e., nitrites and nitrates, and plasma ET-1 in 19 healthy neonates at birth (cord blood) and at ages 5 and 30 days. The sums of serum nitrite and nitrate (NO_x) levels were 27.5 ± 12.8,53.8 ± 14.2, and 38.3 ± 13.2 μmol/l at birth, age 5 days, and age 30 days, respectively. The plasma ET-1 concentrations were 3.9 ± 1.6, 1.1 ± 0.2, and 1.1 ± 0.2 × 10⁶ μmol/l at birth, age 5 days, and age 30 days, respectively. These changes in healthy neonates suggest the presence of active physiological roles for NO and ET-1 in circulatory adaptation to extra-uterine life.

Stable Precursor Fragments of Vasoactive Peptides in Umbilical Cord Blood of Term and Preterm Infants

“…Previous reports had demonstrated high umbilical cord blood levels of ET-1 which were even more pronounced in newborns with birth asphyxia [19,20] leading to a significant negative correlation between ADM levels and pH in cord blood [21]. These observations could indicate that birth stress may be an acute stimulus for the production of ADM and ET-1 in vascular endothelium.…”

Postnatal changes in pulmonary vein responses to endothelin-1 in the normal and chronically hypoxic lung

“…Endo et al (8) found plasma ET-1 concentrations to be threefold higher at birth compared with 5 or 30 days in healthy human neonates, and similar changes have been described in piglets (21). ET-1 blood levels are elevated in patients with pulmonary hypertension and decrease following resolution in persistent pulmonary hypertension of the newborn (24), pulmonary hypertension due to congenital heart disease (18), and pulmonary hypertension due to acute lung injury (19).…”

“…This study suggests that pulmonary veins are involved in postnatal adaptation and the pathogenesis of pulmonary hypertension. postnatal adaptation; pulmonary hypertension A NUMBER OF ANIMAL AND HUMAN studies suggest a role for endothelin-1 (ET-1) in adaptation to extrauterine life (8,21) and in the pathogenesis of pulmonary hypertension (18). Endo et al (8) found plasma ET-1 concentrations to be threefold higher at birth compared with 5 or 30 days in healthy human neonates, and similar changes have been described in piglets (21).…”

Microcirculation of the Newborn

“…In the pulmonary vasculature, ET A -mediated contraction decreases and ET B1 -mediated NO-dependent relaxation increases with advancing postnatal age [34], suggesting a switch from a constricted to dilated state, which follows the known decrease in pulmonary vascular resistance following birth, allowing for blood oxygenation [35]. In line with this, plasma ET-1 levels peak immediately after birth and then gradually decrease, with concentrations in healthy term newborns more than threefold greater than at 5 or 30 days postnatal age [36][37][38]. In a recent study of preterm newborns [23], a significant increase of ET-1 after birth was observed in very preterm neonates, but not in more mature neonates.…”