Oxygen-induced tension in the sheep ductus arteriosus: effects of gestation on potassium and calcium channel regulation.
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 CaL-channel activity could account for the developmental differences in oxygen-induced tension. In the mature ductus, KV-channels appear to be the only K+-channels that oppose ductus tension. Oxygen concentrations between (2% and 15%) inhibit KV-channel activity, which increases the CaL-channel-mediated increase in tension. Low oxygen concentrations have a direct inhibitory effect on CaL-channel activity in the immature ductus; this is not the case in the mature ductus. In the immature ductus, three different K+-channel activities (KV, KCa, and KATP) 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 (>or=30% O2) constrict the ductus by using calcium-dependent pathways that are independent of K+- and CaL-channel activities. Super-physiologic oxygen concentrations eliminate the difference in tensions between the two age groups.
Waleh
Nahid
N
Pharmaceutical Discovery Division, SRI International, Menlo Park, California 94025, USA.
Reese
Jeff
J
Kajino
Hiroki
H
Roman
Christine
C
Seidner
Steven
S
McCurnin
Donald
D
Clyman
Ronald I
RI
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D004373:Ductus Arteriosus / Q000502:physiology*; D005333:Fetus / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D005865:Gestational Age; D010100:Oxygen / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000378:metabolism*; D012756:Sheep; D018709:Statistics, Nonparametric; D014661:Vasoconstriction / Q000502:physiology*
D015220:Calcium Channels; D015221:Potassium Channels; D010100:Oxygen