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 μM), KRB buffer, and KRB buffer containing Px to which progressively increasing concentrations of AA-2414 were added (1 × 10−8 to 1 × 10−4 mol/l). In study 2, placental cotyledons (n = 6) were perfused with control KRB buffer, Px alone, KRB buffer, 1 × 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 F1α. 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 × 10−5 mol/l completely inhibited Px-induced vasoconstriction and increases in lipid peroxide and TXB2secretion rates, but only partially inhibited the increase in 6-keto prostaglandin F1α 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.
Footnotes
-
Send reprint requests to: Scott W. Walsh, Ph.D., Virginia Commonwealth University, Department of Obstetrics and Gynecology, P.O. Box 980034, Richmond, VA 23298-0034. E-mail: swwalsh{at}hsc.vcu.edu
-
↵1 Supported by TAP Holdings, Inc. and Grant HD20973 from the National Institute of Child Health and Human Development. Presented at the 43rd Annual Meeting of the Society for Gynecologic Investigation, March 20–23, 1996, Philadelphia, PA.
- Abbreviations:
- ET
- endothelin
- F
- fetal
- 6-keto PGF1α
- 6-keto prostaglandin F1α
- KRB
- Krebs Ringer bicarbonate
- M
- maternal
- Px
- t-butyl hydroperoxide
- TXB2
- thromboxane B2
- Received September 9, 1998.
- Accepted March 10, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|