Oxygen-Induced Tension in the Sheep Ductus Arteriosus: Effects of Gestationon Potassium and Calcium Channel Regulation

Abstract

Compared with the full-term ductus arteriosus, the premature ductus is less likely to constrict when exposed to postnatal oxygen concentrations. We used isolated fetal sheep ductus arteriosus (pretreated with inhibitors of prostaglandin and nitric oxide production) to determine whether changes in K⁺– and Ca_L-channel activity could account for the developmental differences in oxygen-induced tension. In the mature ductus, K_V-channels appear to be the only K⁺-channels that oppose ductus tension. Oxygen concentrations between (2% and 15%) inhibit K_V-channel activity, which increases the Ca_L-channel-mediated increase in tension. Low oxygen concentrations have a direct inhibitory effect on Ca_L-channel activity in the immature ductus; this is not the case in the mature ductus. In the immature ductus, three different K⁺-channel activities (K_V, K_Ca, and K_ATP) oppose ductus tension and contribute to its decreased tone. Oxygen inhibits the activities of all three K⁺-channels. The inhibitory effects of the three K⁺-channel activities decline with advancing gestation. The decline in K⁺-channel activity is not due to decreased K⁺-channel expression. Super-physiologic oxygen concentrations (≥30% O₂) constrict the ductus by using calcium-dependent pathways that are independent of K⁺– and Ca_L-channel activities. Super-physiologic oxygen concentrations eliminate the difference in tensions between the two age groups.