Heterogeneity in Prostacyclin and Thromboxane Synthesis in Ovine Pulmonary Vascular Tree: Effect of Age and Oxygen Tension

Abstract

Intrapulmonary arteries and veins of 8 near-term fetal lambs (141–145 days gestation) and 8 ewes were isolated into segments of >3mm, 1–3 mm, and < mm in diameter. Vessels were incubated in Krebs' buffer at 37°C at Po₂ ∼100 torr (normoxia) and Po₂ < 50 torr (hypoxia) to study local vascular production of prostanoids. Prostacyclin and thromboxane (Tx) A₂ produced were measured by radioimmunoassay and expressed in ng/mg dry wt, means ± SEM. During normoxia, fetal arteries > 3 mm synthesized more prostacyclin than adult arteries of the same size (1.71 ± 0.3 us 0.45 ± 0.04). However, fetal arteries < 1 mm synthesized less prostacyclin than adult arteries <1 mm (0.47 ± 0.1 vs 1.75 ± 0.16). Prostacyclin production by veins >3 mm was similar in the fetus and adult (0.49 ± 0.06 us 0.67 ± 0.08), but in veins <1 mm was greater in adult than in fetal vessels (1.73 ± 0.17 us 0.54 ± 0.06). Hypoxia-attenuated prostacyclin production by fetal arteries and veins of all sizes, but only in 1 to 3-mm-size adult arteries. In general, production of TxA₂ by segments of fetal and adult vessels was less than 50% of that of prostacyclin. Protein and DNA concentrations in similar sized fetal and adult vessels were similar. The data show that there is heterogeneity in the production of prostacyclin and TxA₂ along the ovine pulmonary vascular tree. Prostanoid synthesis of fetal vessels is markedly influenced by hypoxia, with a greater suppression of prostacyclin synthesis. Similar protein and DNA concentrations in fetal and adult vessels suggest that differences in prostanoid production by vessel segments my be due to differences in enzyme activity rather than cell number or tissue muss.

Key Words:

• DNA
• prostacyclin
• protein
• pulmonary arteries
• pulmonary veins
• thromboxane A₂