Abstract 2115: Vasopressin 1-a Receptor Antagonism Ameliorates Vasoconstriction Associated With Placental Dysfunction Following Fetal Cardiac Bypass
Background: We had previously shown that vasopressin levels rise by 100-fold with fetal bypass, suggesting a possible role in rising placental vascular resistance seen with fetal cardiac surgery. To test our hypothesis that vasopressin may play a central role in placental dysfunction following fetal bypass, we carried out isolated vessel bath studies with placental vasculature, using vasopressin and selective vasopressin receptor antagonism (V1-a).
Methods: Adult rat aortas (controls) and fourth order ovine placental vessels were harvested and 5 mm rings mounted in temperature controlled aerated Radnoti vessel baths with continuous isometric tension measurement and recording. All vessels were tested with phenylephrine and acetylcholine to demonstrate viability of endothelium and baseline vascular smooth muscle responses. Placental vessels (n=6) and rat aortas (n=8) were exposed to log doses of vasopressin (10−11 to 10−7 g/mL). Placental vessels (n=5) and rat aortas (n=4) were treated with V1-a receptor antagonist and exposed to the same log doses of vasopressin. Changes in vascular tension are represented as percent change from baseline, mean ± SD.
Results: Placental and aortic vessels both had a bi-phasic response to increasing doses of vasopressin initially dilating (2.1±9.1%) at the 10−11 g/mL dose and (−11.1±3.9%) at the 10−10 g/mL, respectively. Followed by incremental increases in constriction, most profound at the 10−8 g/mL dose (36.7±22.7%; in-group ANOVA p = 0.009, Post Hoc p = 0.001) for placental and 10−7 g/mL dose (37.8±20.8%, in-group ANOVA p = 0.101, Post Hoc p = 0.016) for aortic vessels. V1-a receptor antagonism completely blocked vasopressin induced constriction when the antagonist to agonist ratio was greater than equal to 100:1 (ANOVA p < 0.002). A 1:1 antagonist to agonist ratio reduced vascular tension by 39±14% and 32±19, for placental and aortic vessels respectively.
Conclusion: Placental vasculature has a biphasic response to vasopressin as seen in systemic vasculature. Vasopressin 1-a receptor antagonism can completely inhibit vasopressin induced placental vasoconstriction. V1a antagonism may provide a powerful strategy to overcome increased placental vascular resistance following fetal cardiac surgery.