Gestational changes in pulmonary converting enzyme activity in the fetal rabbit.

Abstract

SUMMARY Changes in angiotensin-converting enzyme were measured in the lungs of fetal rabbits isolated and perfused in situ at varying ages from 22 days gestation to 7 days of age under controlled conditions of flow, pH, and temperature. Enzyme activity was assessed by infusing bradykinin or angiotensin I in Krebs-Henseleit solution and measuring residual peptide in the effluent by radioimmunoassay. The levels of substrate studied were below those required for enzyme saturation. Lungs of 22 day gestation fetuses removed only one-third of either peptide. The activity at term and in neonatal life resulted in more than 80% peptide removal. The time of the greatest rise in the percent substrate cleared occurs earlier than the time of the greatest increase in lung and body weight. The lower percentage of substrate cleared in early gestation appears to result in part from a limited surface area for enzyme activity in the primitive fetal pulmonary microvascular bed, since morphological studies with fluorescein-tagged anticonverting enzyme antibody demonstrated the presence of enzyme in the lung as early as 17 days of gestation. Electron micrographs of the pulmonary endothelial cell surface reveal that the degree of surface infolding and hence surface area increases with gestation. The higher percentage of substrate cleared in later gestation closely parallels the structural and ultrastructural development of the vascular bed. The presence of converting enzyme in the placenta by the second third of gestation and the large size of the placenta suggest that this organ may be a major locus of converting enzyme activity in the fetus.IMMATURITY of the lung and the consequent predisposition to neonatal respiratory distress syndrome (RDS) is a great risk to the survival of the prematurely born infant. In view of the role of the lungs in the clearance, activation, and release of vasoactive substances, 1 we hypothesized that immaturity of these functions prior to term birth is important in the pathogenesis of RDS, especially in the disorders of circulatory regulation and water balance seen in this disease. 2 Converting enzyme, a peptidyldipeptide hydrolase (EC 3.4.15.1) located on the plasma membrane of endothelial cells, degrades bradykinin (BK) and activates angiotensin I (A I) to angiotensin II (A II). 3 Both peptides have been assigned important roles in neonatal circulatory adaptations and transvascular fluid balance. 4 " 7 Studies in the fetal lamb have suggested a deficiency in converting enzyme in the fetus, 8 uration of converting enzyme activity in the lungs of fetal rabbits during the last third of gestation, and related this to the distribution of the enzyme as previously determined by immunofluorescence"' and to the complexity of the endothelial cell surface as revealed by electron micrographic techniques. MethodsOne hundred and one fetal New Zealand white rabbits, ranging in weight from 4 to 60 g, were obtained from 34 timed pregnancies and were studied at 22, 24, 25, 26, 28, 29, and 30 days of gestation. The fet...

Lung Metabolism of Eicosanoids: Prostaglandins, Prostacyclin, Thromboxane, and Leukotrienes

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Perinatal Development of Angiotensin – Converting Enzyme in the Rat’s Blood

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