Vol. 290, Issue 1, 220-226, July 1999

AA-2414, an Antioxidant and Thromboxane Receptor Blocker, Completely Inhibits Peroxide-Induced Vasoconstriction in the Human Placenta¹

Scott W. Walsh, Yuping Wang and Anthony Killian

Departments of Obstetrics and Gynecology, and Physiology, Virginia Commonwealth University, Medical College of Virginia, Richmond, Virginia

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 µM), KRB buffer, and KRB buffer containing Px to which progressively increasing concentrations of AA-2414 were added (1 × 10⁸ to 1 × 10⁴ mol/l). In study 2, placental cotyledons (n = 6) were perfused with control KRB buffer, Px alone, KRB buffer, 1 × 10⁵ 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 F₁. 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 × 10⁵ 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 F₁ 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.