1. Academic Validation
  2. AA-2414, an antioxidant and thromboxane receptor blocker, completely inhibits peroxide-induced vasoconstriction in the human placenta

AA-2414, an antioxidant and thromboxane receptor blocker, completely inhibits peroxide-induced vasoconstriction in the human placenta

  • J Pharmacol Exp Ther. 1999 Jul;290(1):220-6.
S W Walsh 1 Y Wang A Killian
Affiliations

Affiliation

  • 1 Departments of Obstetrics and Gynecology, and Physiology, Virginia Commonwealth University, Medical College of Virginia, Richmond, Virginia, USA. swwalsh@hsc.vcu.edu
PMID: 10381779
Abstract

We hypothesized that AA-2414, a novel thromboxane receptor blocker with antioxidant properties, would inhibit peroxide-induced vasoconstriction in the isolated perfused human placental cotyledon. In study 1, placental cotyledons (n = 5) were perfused serially for 20- min intervals with control KrebsRinger-bicarbonate (KRB) buffer, t-butyl hydroperoxide (Px; 100 microM), KRB buffer, and KRB buffer containing Px to which progressively increasing concentrations of AA-2414 were added (1 x 10(-8) to 1 x 10(-4) mol/l). In study 2, placental cotyledons (n = 6) were perfused with control KRB buffer, Px alone, KRB buffer, 1 x 10(-5) mol/l AA-2414 alone, Px plus AA-2414, and Px alone. Compared with control, perfusion with Px significantly increased perfusion pressure, vascular resistance, and the maternal and fetal secretion rates of lipid peroxides, thromboxane B2 (TXB2) and 6-keto prostaglandin F1alpha. In study 1, AA-2414 + Px produced a dose-response inhibition of Px-induced increases in perfusion pressure, vascular resistance, and maternal secretion of lipid peroxides and TXB2. In study 2, perfusing AA-2414 at a dose of 1 x 10(-5) mol/l completely inhibited Px-induced vasoconstriction and increases in lipid peroxide and TXB2 secretion rates, but only partially inhibited the increase in 6-keto prostaglandin F1alpha secretion. We conclude that AA-2414 inhibited peroxide-induced vasoconstriction in the human placenta, as well as peroxide- induced increases in the placental secretion rates of lipid peroxides and thromboxane, but only partially inhibited peroxide-induced increases in the placental secretion rate of prostacyclin.

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