Vasodilatory response of fetoplacental vasculature to adrenomedullin afterconstriction with the thromboxane sympathomimetic U46619

OBJECTIVE: This study was undertaken to determine whether adrenomedullin, a hypotensive peptide, decreases vasomotor tone in fetoplacental vasculature that has been constricted with the thromboxane sympathomimetic U46619. STUDY DESIGN: The fetoplacental vascular beds of 20 perfused human placenta l cotyledons were vasoconstricted with a continuous infusion of U46619 (10( -8) mol/L). The vasculature was then sequentially injected with deionized w ater, 30 ng adrenomedullin, 300 ng adrenomedullin, and 3000 ng adrenomedull in. Any change in perfusion pressure was noted after each dose. In a separa te experiment the fetoplacental vasculature in 2 perfused cotyledons from e ach of 10 placentas was vasoconstricted with U46619 (10(-8) mol/L). Adrenom edullin was infused continuously at either 200 ng/min (n = 5) or 2000 ng/mi n (n = 5) for 40 minutes. A corresponding control cotyledon from each place nta had isoionic sodium chloride solution added to its per fusion. Perfusio n pressures were recorded every minute during the infusion and for 40 minut es afterward. Analysis of variance was used to compare pressure changes in the cotyledons that received bolus doses of adrenomedullin. Paired t tests of mean percentage pressure changes were used to compare the study and cont rol groups that received the continuous infusions. RESULTS: In the cotyledons that received bolus doses of adrenomedullin, the mean (+/-SEM) percentage perfusion pressure changes from the baseline were -6.7 +/- 0.5 for 30 ng adrenomedullin (P = .0039), -8.5 +/- 0.7 for 300 ng adrenomedullin (P < .0001), and -13.1 +/- 1.0 for 3000 ng adrenomedullin ( P < .0001). With the continuous adrenomedullin infusion of 200 ng/min, ther e was no significant difference in the mean percentage pressure change from baseline between the study and control groups (-0.57%). At 2000 ng/min the re was a significant difference (-15.34%; P < .0001). CONCLUSION: Adrenomedullin caused vasodilatation of fetoplacental vasculatu re previously constricted with the thromboxane sympathomimetic U46619 in th e isolated perfused placental cotyledon. This vasodilatation occurred in a dose-dependent manner.