Large conductance Ca2+-activated and voltage-activated K+ channels contribute to the rise and maintenance of estrogen-induced uterine vasodilation and maintenance of blood pressure.
Uterine blood flow (UBF) increases greater than 4-fold 90 min after systemic estradiol-17β (E2β) in nonpregnant sheep and remains elevated longer than 6-8 h; mean arterial pressure (MAP) is unchanged. Large-conductance Ca(+2)-activated (BK(Ca)) and voltage-activated (K(V)) K(+) channels contribute to the acute rise in UBF; their role in maintaining UBF and MAP longer than 90 min is unknown. We examined this in five nonpregnant, ovariectomized ewes with uterine artery (UA) flow probes and catheters in a UA for infusion of K(+) channel inhibitors and uterine vein to sample venous effluent. Animals received systemic E2β (1.0 μg/kg; control), E2β+UA tetraethylammonium (TEA; 0.4-0.8 mm, n = 4), and E2β+UA 4-aminopyridine (4-AP; 0.01-0.08 mm, n = 4) to block BK(Ca) and K(V), respectively, while monitoring MAP, heart rate, and UBF. Uterine cGMP synthesis was measured. Ninety minutes after E2β, UBF rose 4.5-fold, uterine vascular resistance (UVR) fell greater than 5-fold and MAP was unchanged [78 ± 0.8 (sem) vs. 77 ± 1.5 mm Hg] in control studies and before UA inhibition with TEA and 4-AP. Between 90 and 120min, UBF, UVR, and MAP were unchanged after E2β alone. E2β+TEA dose dependently decreased ipsilateral UBF and increased UVR (24 ± 8.9 and 38 ± 16%, respectively, at 0.8 mm; P < 0.03); MAP was unchanged. Contralateral UBF/UVR were unaffected. E2β+4-AP also dose dependently decreased ipsilateral UBF and increased UVR (27 ± 5.3 and 76 ± 18%, respectively, at 0.08 mm; P < 0.001); however, MAP rose 27 ± 6.9% (P ≤ 0.006). E2β increased uterine cGMP synthesis greater than 3.5-fold and was unaffected by local K(+) channel inhibition. BK(Ca) and K(V) contribute to the rise and maintenance of E2β-induced uterine vasodilation, which is partially cGMP dependent. Systemic vascular K(V) also contributes to maintaining MAP after systemic E2β.
Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9063, USA. charles.rosenfeld@utsouthwestern.edu
Charles R
CR
Rosenfeld
Timothy
T
Roy
D000818:Animals; D062186:Arterial Pressure; D001794:Blood Pressure; D006152:Cyclic GMP / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006439:Hemodynamics; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal; D012039:Regional Blood Flow; D012756:Sheep; D014599:Uterus / Q000098:blood supply* / Q000473:pathology*; D014664:Vasodilation
D004967:Estrogens; D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D006152:Cyclic GMP