title: Regulation of transplacental water transfer: the role of fetoplacental venous tone.
abstract: We used the in vitro dually perfused human placental lobule to test the hypothesis that known vasoconstrictors of the fetal placental circulation, angiotensin II and the thromboxane mimetic U46619 could induce fetomaternal water transfer. Secondly, we used a combination of vasoconstrictor and mechanically induced increases in fetal placental circulatory pressure to examine the role of the venous system in this context. Fetal-side administration of angiotensin II (A-II) and U46619 (n=6 and n=9, for A-II and U46619, respectively) induced dose dependent, recoverable elevations in fetal inflow hydrostatic pressure (HP; A-II: maximum contractility=83 mmHg, EC50=22.0 nM; U46619: maximum contractility was not achieved, but exceeded the A-II effect) and loss of perfusate from the fetal side (A-II: EC50=70.2 nM, maximum fetal-side solvent loss=1906 microl/min; U46619: maximum fetal-side solvent loss was not achieved, but exceeded the A-II effect). Fetal-side solvent loss, for both agonists, was correlated linearly with fetomaternal inflow HP (FMIHP) in a biphasic manner (between 0 and 30 mmHg the slopes (+/-S.E.) were 6.4+/-2.2 and 17.1+/-5.8 microl/(min mmHg) for A-II and U46619, respectively; between 30 and 70 mmHg the slopes (+/-S.E.) were 35.6+/-6.5 and 43.7+/-15.9 microl/(min mmHg) for A-II and U46619, respectively). Increasing fetal-side lumenal pressure (n=3) by raising the fetal outflow catheter caused a loss of perfusate from the fetal side which was reduced in the presence of U46619 (fetal solvent loss per unit increase in fetal-side inflow HP: slopes were 1.198+/-0.123 and 0.783+/-0.085 microl/(min mmHg mmHg), respectively). Notwithstanding the possibility of fetoplacental arterial constriction, we conclude that vasoconstrictive agonists in the fetoplacental circulation affect venous resistance, causing fetomaternal fluid loss. These observations could be relevant to the oligohydramnios associated with intrauterine growth restriction, a condition associated with increased resistance in the umbilical circulation.
authors.affiliation: Division of Human Development, The Medical School, University of Manchester, St. Mary's Hospital, Hathersage Road, Manchester, M13 0JH, UK. paul.brownbill@mancester.ac.uk
authors.forename: P
authors.initials: P
authors.lastname: Brownbill
authors.forename: C P
authors.initials: CP
authors.lastname: Sibley
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006874:Hydrostatic Pressure; D066298:In Vitro Techniques; D010477:Perfusion; D010920:Placenta / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D021041:Placental Circulation / Q000502:physiology*; D011247:Pregnancy; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014680:Veins / Q000187:drug effects / Q000502:physiology*; D014690:Venous Pressure / Q000187:drug effects / Q000502:physiology*; D014867:Water / Q000378:metabolism*
chemical_list: D014662:Vasoconstrictor Agents; D014867:Water; D000804:Angiotensin II; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid