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-induced rises in uterine blood flow in ovine
pregnancy
1 Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9063; and 2 Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota 55455
Uterine blood flow (UBF) increases >30-fold
during ovine pregnancy. During the last trimester, this reflects
vasodilation, which may be due to placentally derived estrogens. In
nonpregnant ewes, estradiol-17
(E2) increases UBF
>10-fold by activating nitric oxide synthase and large conductance
calcium-dependent potassium channels (BKCa). To determine
whether BKCa channels modulate basal and
E2-induced increases in UBF, studies were performed in
near-term pregnant ewes with uterine artery flow probes and catheters
for intra-arterial infusions of tetraethylammonium (TEA), a selective
BKCa channel antagonist at <1 mM, in the absence or
presence of E2 (1 µg/kg iv). Uterine arteries were
collected to measure BKCa channel mRNA. TEA (0.15 mM)
decreased basal UBF (P < 0.0001) 40 ± 8% and
55 ± 7% (n = 11) at 60 and 90 min, respectively, and increased resistance 175 ± 48% without affecting
(P > 0.1) mean arterial pressure (MAP), heart rate, or
contralateral UBF. Systemic E2 increased UBF 30 ± 6% and heart rate 13 ± 1% (P 
0.0001, n = 13) without altering MAP. Local TEA (0.15 mM)
inhibited E2-induced increases in UBF without affecting
increases in heart rate (10 ± 4%; P = 0.006).
BKCa channel mRNA was present in uterine artery myocytes
from pregnant and nonpregnant ewes. Exponential increases in ovine UBF
in late pregnancy may reflect BKCa channel activation,
which may be mediated by placentally derived estrogens.
estradiol-17; sheep; smooth muscle
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