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 F(1α) (6-keto-PGF(1α)). Synthesis of 6-keto-PGF(1α) was de novo, since aspirin inhibited its formation. P and early uterine arteries produced more 6-keto-PGF(1α) than NP and late vessels (P < 0.05): 386 ± 60 (X̄ ± SE) and 175 ± 23 vs. 32 ± 5 and 18 ± 4 pg/mg·h, respectively. A similar relationship was observed for omental arteries: 101 ± 14 and 74 ± 14 vs. 36 ± 10 and 22 ± 4 pg/mg·h, respectively. Furthermore, synthesis by arteries from P and early animals was greater in uterine than omental vessels (P < 0.05); this was not observed in NP or late vessels. ANG II increased 6-keto-PGF(1α) 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-PGF(1α) 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.
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