Magness R R, Osei-Boaten K, Mitchell M D, Rosenfeld C R
J Clin Invest. 1985 Dec;76(6):2206-12. doi: 10.1172/JCI112229.
Normal pregnancy is associated with reduced systemic pressor responses to infused angiotensin II (ANG II); furthermore, the uterine vascular bed is even less responsive to vasoconstriction by ANG II than the systemic vasculature overall. The mechanism(s) for this refractoriness remains unknown. To determine if vessel production of prostacyclin may be responsible, uterine and omental artery segments were obtained from four groups of sheep, nonpregnant (NP), pregnant (P; 131 +/- 4 d), early postpartum (2.2 +/- 0.4 d), and late postpartum (16 +/- 2 d), and incubated in Krebs-Henseleit alone or with ANG II in the absence or presence of Saralasin. Prostacyclin was measured as 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). Synthesis of 6-keto-PGF1 alpha was de novo, since aspirin inhibited its formation. P and early uterine arteries produced more 6-keto-PGF1 alpha than NP and late vessels (P less than 0.05): 386 +/- 60 (X +/- SE) and 175 +/- 23 vs. 32 +/- 5 and 18 +/- 4 pg/mg X h, respectively. A similar relationship was observed for omental arteries: 101 +/- 14 and 74 +/- 14 vs. 36 +/- 10 and 22 +/- 4 pg/mg X h, respectively. Furthermore, synthesis by arteries from P and early animals was greater in uterine than omental vessels (P less than 0.05); this was not observed in NP or late vessels. ANG II increased 6-keto-PGF1 alpha production 107 +/- 20% and 92 +/- 16% in P and early uterine arteries only; the threshold dose was between 5 X 10(-11) and 5 X 10(-9) M ANG II. This ANG II-induced increase in 6-keto-PGF1 alpha by uterine arteries was inhibited by Saralasin, which by itself had no effect. During pregnancy, the reduced systemic pressor response to ANG II and the even greater refractoriness of the uterine vascular bed may be reflective of vessel production of the potent vasodilator, prostacyclin. Furthermore, in the uterine vasculature, this antagonism may be potentiated by specific ANG II receptor-mediated increases in prostacyclin.
正常妊娠与输注血管紧张素 II（ANG II）时全身升压反应降低有关；此外，子宫血管床对 ANG II 引起的血管收缩反应比整个全身血管系统更不敏感。这种不应性的机制尚不清楚。为了确定前列环素的血管生成是否可能是原因，从四组绵羊中获取子宫和网膜动脉段，分别为未怀孕（NP）、怀孕（P；131±4 天）、产后早期（2.2±0.4 天）和产后晚期（16±2 天），并将其单独置于 Krebs-Henseleit 溶液中或与 ANG II 一起在有无沙拉新的情况下孵育。前列环素以 6-酮-前列腺素 F1α（6-酮-PGF1α）来测量。6-酮-PGF1α 的合成是从头合成，因为阿司匹林会抑制其形成。怀孕和产后早期的子宫动脉产生的 6-酮-PGF1α 比未怀孕和产后晚期的血管更多（P<0.05）：分别为 386±60（X±SE）和 175±23 与 32±5 和 18±4 pg/mg×h。网膜动脉也观察到类似的关系：分别为 101±14 和 74±14 与 36±10 和 22±4 pg/mg×h。此外,怀孕和产后早期动物的动脉在子宫中的合成比在网膜血管中更大（P<0.05）；在未怀孕或产后晚期的血管中未观察到这种情况。ANG II 仅使怀孕和产后早期子宫动脉中的 6-酮-PGF1α 的产生增加 107±20%和 92±16%；阈值剂量在 5×10⁻¹¹ 至 5×10⁻⁹ M 的 ANG II 之间。子宫动脉中这种由 ANG II 诱导的 6-酮-PGF1α 的增加被沙拉新抑制，而沙拉新本身没有作用。在怀孕期间，对 ANG II 的全身升压反应降低以及子宫血管床更大的不应性可能反映了强效血管舒张剂前列环素的血管生成。此外，在子宫血管系统中，这种拮抗作用可能通过特定的 ANG II 受体介导的前列环素增加而增强。
