Magness R R, Rosenfeld C R
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063.
Endocrinology. 1993 Jun;132(6):2445-52. doi: 10.1210/endo.132.6.8389281.
Refractoriness to angiotensin-II (ANG II)-induced vasoconstriction is greater in the uteroplacental vs. systemic vascular beds during pregnancy, possibly reflecting enhanced uterine artery prostacyclin production. We determined the role(s) of calcium and calcium channels in regulating basal and ANG II-induced vascular prostacyclin production in uterine and omental (systemic) arteries obtained from pregnant (P) and nonpregnant (NP) ewes. To evaluate the endothelial contribution to basal and stimulated prostacyclin production, arteries with and without endothelium also were incubated in the absence and presence of 50 nM ANG II, 5 microM A23187, or 5 microM arachidonate. Basal prostacyclin production by intact and denuded uterine and systemic arteries was P > NP (P < 0.05), plus in intact arteries, production fell approximately 33% in calcium-free Krebs-Henseleit and 5 microM EGTA. Although basal prostacyclin production by P and NP uterine and NP systemic arteries was unaffected by 5 microM verapamil, P systemic artery synthesis fell 41% (P < 0.05). P uterine artery prostacyclin production increased similarly with ANG II (61%) and A23187 (78%) in the presence of calcium (2 mM), whereas NP uterine arteries responded only to A23187 (71%). Verapamil inhibited ANG II-induced increases in prostacyclin synthesis by P uterine arteries. Neither calcium removal nor verapamil altered prostacyclin responses to arachidonate (5 microM). The endothelium accounted for approximately 68% of basal prostacyclin production by all arteries studied and for 100% of ANG II-induced increases by P uterine arteries (P < 0.01). A23187 and arachidonate increased both endothelial and smooth muscle prostacyclin production (P < 0.01). During ovine pregnancy, extracellular calcium entry via activation of potential-gated calcium channels are involved in modulating basal vascular prostacyclin production as well as ANG II-induced increases in uterine artery production. Furthermore, the endothelium is the primary source of basal vascular prostacyclin synthesis and the sole source of ANG II-stimulated increases by uterine arteries during pregnancy.
在孕期，子宫胎盘血管床对血管紧张素 II（ANG II）诱导的血管收缩的抵抗性大于体循环血管床，这可能反映出子宫动脉前列环素生成增加。我们确定了钙和钙通道在调节从怀孕（P）和未怀孕（NP）母羊获取的子宫和网膜（体循环）动脉中基础和ANG II诱导的血管前列环素生成中的作用。为了评估内皮细胞对基础和刺激的前列环素生成的贡献，有内皮和无内皮的动脉也在不存在和存在50 nM ANG II、5 μM A23187或5 μM花生四烯酸的情况下进行孵育。完整和去内皮的子宫和体循环动脉的基础前列环素生成量为P > NP（P < 0.05），此外，在完整动脉中，在无钙的Krebs-Henseleit溶液和5 μM EGTA中，生成量下降约33%。尽管P和NP子宫动脉以及NP体循环动脉的基础前列环素生成不受5 μM维拉帕米的影响，但P体循环动脉的合成下降了41%（P < 0.05）。在存在钙（2 mM）的情况下，P子宫动脉前列环素生成对ANG II（61%）和A23187（78%）的反应相似，而NP子宫动脉仅对A23187（71%）有反应。维拉帕米抑制P子宫动脉中ANG II诱导的前列环素合成增加。去除钙和维拉帕米均未改变前列环素对花生四烯酸（5 μM）的反应。内皮细胞占所有研究动脉基础前列环素生成的约68%，占P子宫动脉ANG II诱导增加量的100%（P < 0.01）。A23187和花生四烯酸增加了内皮细胞和平滑肌的前列环素生成（P < 0.01）。在绵羊孕期，通过激活电压门控钙通道使细胞外钙内流参与调节基础血管前列环素生成以及ANG II诱导的子宫动脉生成增加。此外，内皮细胞是基础血管前列环素合成的主要来源，也是孕期子宫动脉ANG II刺激增加的唯一来源。
