Vasodilatory response of fetoplacental vasculature to adrenomedullin after constriction 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.


METHODS
The fetoplacental vascular beds of 20 perfused human placental cotyledons were vasoconstricted with a continuous infusion of U46619 (10(-8) mol/L). The vasculature was then sequentially injected with deionized water, 30 ng adrenomedullin, 300 ng adrenomedullin, and 3000 ng adrenomedullin. Any change in perfusion pressure was noted after each dose. In a separate experiment the fetoplacental vasculature in 2 perfused cotyledons from each of 10 placentas was vasoconstricted with U46619 (10(-8) mol/L). Adrenomedullin was infused continuously at either 200 ng/min (n = 5) or 2000 ng/min (n = 5) for 40 minutes. A corresponding control cotyledon from each placenta had isotonic sodium chloride solution added to its perfusion. Perfusion pressures were recorded every minute during the infusion and for 40 minutes 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 control 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, there was no significant difference in the mean percentage pressure change from baseline between the study and control groups (-0.57%). At 2000 ng/min there was a significant difference (-15.34%; P <.0001).


CONCLUSIONS
Adrenomedullin caused vasodilatation of fetoplacental vasculature previously constricted with the thromboxane sympathomimetic U46619 in the isolated perfused placental cotyledon. This vasodilatation occurred in a dose-dependent manner.
Hoeldtke
N J
NJ
Department of Obstetrics and Gynecology, Madigan Army Medical Center, Tacoma, WA, USA.
Wagner
R K
RK
Calhoun
B C
BC
Hume
R F
RF
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D053607:Adrenomedullin; D001808:Blood Vessels / Q000187:drug effects* / Q000196:embryology*; D005260:Female; D005333:Fetus / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D010455:Peptides / Q000494:pharmacology*; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D013566:Sympathomimetics / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology*
D010455:Peptides; D013566:Sympathomimetics; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D053607:Adrenomedullin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid