title: The Effects of Vasopressin and Oxytocin on the Fetoplacental Distal Stem Arteriolar Vascular Resistance of the Dual-Perfused, Single, Isolated, Human Placental Cotyledon.
abstract: Vasoactive agents administered to counter maternal hypotension at cesarean delivery may theoretically intensify the hypoxemic fetoplacental vasoconstrictor response and, hence, negatively impact transplacental oxygen delivery to the fetus. Yet, this aspect of their pharmacodynamic profiles is seldom mentioned, let alone investigated. We hypothesized that vasopressin, a potent systemic vasoconstrictor, and oxytocin, a uterotonic agent administered routinely at cesarean delivery, which, in contrast to vasopressin, possesses significant systemic vasodilator properties, would not influence distal stem villous arteriolar resistance.
  
  
  
  The dual-perfused, single, isolated cotyledon, human placental perfusion model was used to examine the resistance response of the fetoplacental circulation to oxytocin and vasopressin in placentae harvested from healthy women. Twelve of a total of 17 individual experiments were conducted successfully during which either oxytocin (n = 6) or vasopressin (n = 6) was introduced into the fetal reservoir in concentration increments of 10 M. Fetoplacental distal stem villous arteriolar perfusion pressure (FAP) was measured continuously. The fetal circuit concentration of either oxytocin or vasopressin was raised in a stepwise fashion from 10 to 10 M or 10 to 10 M, respectively. Both reservoirs were then purged of drug, after which 1-mL 1.0 mM 5-hydroxytryptamine (2.5 µM), an agent well known to manifestly increase fetoplacental distal stem villous arteriolar resistance, was introduced into the fetal circuit. A significant increase in FAP from baseline in response to exposure to 5-hydroxytryptamine confirmed that the fetoplacental vasoconstrictor response remained reactive. The primary outcome of this study was changes in FAP after incremental dosing of vasopressin and oxytocin.
  
  
  
  No changes in FAP were observed with either oxytocin or vasopressin regardless of the drug concentration tested. For each drug and concentration, a mean pressure change greater than ±10 mm Hg was excluded with 95% confidence. In contrast, 5-hydroxytryptamine significantly increased perfusion pressure in all 12 successful experiments.
  
  
  
  Oxytocin and vasopressin do not influence human fetoplacental distal stem villous arteriolar resistance. The neutral impact of vasopressin noted here is thus analogous to the reported negligible influence of the drug on human pulmonary arteriolar resistance. Neither drug seems likely to adversely influence the compensatory hypoxemic fetoplacental vasoconstrictor response.
authors.affiliation: From the Departments of *Anesthesiology and †Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: John W
authors.initials: JW
authors.lastname: Downing
authors.forename: Curtis L
authors.initials: CL
authors.lastname: Baysinger
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Johnson
authors.forename: Ray L
authors.initials: RL
authors.lastname: Paschall
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Shotwell
mesh_terms: D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D009924:Organ Culture Techniques; D010121:Oxytocin / Q000494:pharmacology*; D010477:Perfusion / Q000295:instrumentation / Q000379:methods*; D010920:Placenta / Q000187:drug effects* / Q000502:physiology; D021041:Placental Circulation / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology; D014667:Vasopressins / Q000494:pharmacology*
chemical_list: D014667:Vasopressins; D010121:Oxytocin