Lung catecholamines and cyclic nucleotides during perinatal development in the rat. Possible relationships with...

In this study, we investigated in parallel the evolution of endogenous catecholamine and cyclic nucleotide levels in lung tissue in the course of normal fetal development of the rat from day 17 of gestation to day 10 postpartum; the findings were correlated with the successive stages of lung differentiation. These were assessed morphologically by electron microscopy, and biochemically by measuring the levels of the main lung tissue phospholipids and studying their fatty acid composition. Dopamine levels were low and always remained under 5 ng/g of wet tissue. Nevertheless, slight rises were observed between days 17 and 19 of gestation (1.8 and 2.78 ng/g, respectively) and between days 21 of gestation and birth (2.56 and 4.25 ng/g, respectively). These changes were significant (P less than 0.05). Norepinephrine (NE) levels first decreased by about 50% between days 17 and 19 of gestation (7.34 and 3.88 ng/g, respectively), (P less than 0.01) and then rose sharply about 4 times until birth (17.24 +/- 3.90 ng/g), and more slowly from then on. On day 10 postpartum, the mean NE level was 34.31 +/- 3.28 ng/g. The levels of the two cyclic nucleotides [cyclic adenosine 3':5'-monophosphate and cyclic guanosine 5'-monophosphate (cGMP)] were quite high on day 17 and remained so until day 19 (cAMP = 220 pmoles /g; cGMP = 20 pmoles/g). From day 19 until day 21, the levels of the two nucleotides decreased (cAMP = 140 pmoles/g; cGMP = 8 pmoles/g; P less than 0.05). During this period, the decrease in cGMP level was about twice that of cAMP. During the last day of gestation, the cAMP level was still decreasing, whereas cGMP was increasing. After birth, the levels of the two cyclic nucleotides rapidly increased to day 5. Between days 5 and 10 postpartum, no significant changes were observed in either cAMP or cGMP levels. The time course of the variations reported suggests that they are related to the maturation processes of lung assessed on the basis of morphological and biochemical criteria. On day 19 of gestation, when the first lamellar bodies appear, large changes occur in the evolution of NE and cyclic nucleotide levels, suggesting that these changes may be related to the onset of surfactant synthesis. On day 21 of gestation, the cAMP and cGMP ratio rises sharply; at the same time, the total phospholipid level is increased by 50%. At this stage, lamellar bodies are actively differentiating within type II pneumocytes and massively released into the fetal airways. The relationships between the variations of the studied biochemical parameters and the maturation processes of lung suggest that dopamine and NE could be involved in surfactant synthesis and release via their second messenger, the cyclic nucleotides. Further investigations are needed to elucidate the mechanisms regulating these changes.