Abstract 164 Poster Session II, Sunday, 5/2 (poster 255)

UBF increases 30-fold in ovine pregnancy and is essential for fetal growth and well-being. We previously suggested this rise occurs in 3 phases: 1) pre-implantation reflecting vasodilation, 2) placentation reflecting vascular growth, and 3) post-placentation, which is associated with rapid fetal growth and also reflects vasodilation. The mechanism(s) responsible for vasodilation in phase 3 is unknown. We and others were unable to demonstrate a role for prostaglandins, and acute infusion of the nitric oxide synthase inhibitor L-NAME decreased uterine cGMP secretion, but not UBF ( JCI, 1996). Potassium channels hyperpolarize smooth muscle membranes, resulting in vasodilation. E2 activates KCa, contributing to E2-induced rises in UBF in nonpregnant ewes. Since placental E2 synthesis increases >10-fold in pregnancy, we postulated that enhanced KCa activity might modulate basal uterine vascular tone and contribute to E2-induced rises in UBF in pregnant ewes. 5 pregnant ewes (130-140d gestation) with bilateral uterine artery flow probes and catheters in distal branches of the uterine artery of each horn were studied. Initially, we infused the KCa specific antagonist tetraethylammonium ion (TEA) for 90min via a uterine artery to achieve blood levels of 0.15 mM while monitoring UBF, arterial pressure (MAP) and heart rate (n=11). Local TEA alone did not alter MAP (P=0.11), heart rate (P=0.1), or contralateral UBF (P=0.1), which was 477±71[SEM], 425±113 and 471±81 ml/min before TEA, 90min of infusion and 60min postinfusion, respectively. However, ipsilateral UBF fell from 415±53 to 191±65 ml/min (P<0.0001; 55±7%) then rose to 335±64 ml/min, respectively. Resistance mirrored the fall in UBF, rising from 0.23±0.03 to 0.80±0.18 mmHg·min/ml (P<0.001), then falling to 0.44±0.09, respectively. We next examined the effects of continuous local TEA infusions (0.15 mM) on E2-induced (1 g/kg iv) rises in UBF (n=13). MAP was unaffected by TEA+E2, while heart rate rose 10±4% (P=0.006) at 90min, demonstrating intact systemic responses. Contralateral UBF rose 12±5% (P=0.03) 90min after E2, 505±53 to 552±54 ml/min. Ipsilateral UBF, however, fell 24±7% after 30min of TEA (490±61 to 409 ± 73 ml/min) and was 28±5% below control 90min after E2 (374±63; P<0.0001). Resistance rose 58±14%, P=0.004, 90min after E2. We conclude that KCa modulate uterine vascular tone in ovine pregnancy, accounting for >50% of the vasodilation seen at term. KCa also contributes to E2-induced rises in UBF in pregnant and nonpregnant ewes. We speculate that endogenous placental estrogen may regulate KCa activity in pregnancy, accounting for the third trimester rise in UBF. This work was supported by NIH HD08783.