Ca2+-activated K+ channels modulate basal and E-2 beta-induced rises in uterine blood flow in ovine pregnancy

Uterine blood flow (UBF) increases >30-fold during ovine pregnancy. During the last trimester, this reflects vasodilation, which may be due to placent ally derived estrogens. In nonpregnant ewes, estradiol-17 beta (E(2)beta) i ncreases UBF>10-fold by activating nitric oxide synthase and large conducta nce calcium-dependent potassium channels (BKCa). To determine whether BKCa channels modulate basal and E(2)beta -induced increases in UBF, studies wer e performed in near-term pregnant ewes with uterine artery flow probes and catheters for intra-arterial infusions of tetraethylammonium (TEA), a selec tive BKCa channel antagonist at <1 mM, in the absence or presence of E-2<be ta> (1 mug/kg iv). Uterine arteries were collected to measure BKCa channel mRNA. TEA (0.15 mM) decreased basal UBF (P<0.0001) 40 <plus/minus> 8% and 5 5 +/- 7% (n = 11) at 60 and 90 min, respectively, and increased resistance 175 +/- 48% without affecting (P>0.1) mean arterial pressure (MAP), heart r ate, or contralateral UBF. Systemic E(2)beta increased UBF 30 +/- 6% and he art rate 13 +/- 1% (P less than or equal to 0.0001, n = 13) without alterin g MAP. Local TEA (0.15 mM) inhibited E(2)beta -induced increases in UBF wit hout 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 .