Urinary excretion of prostacyclin in a rat model of uteroplacental vasculature occlusion: implications for fetal growth retardation

Abstract

An experimental model was devised in the pregnant rat to study by a combined high pressure liquid chromatography and radioimmunoassay technique the accumulation of prostanoids (PNs) in the urine after transient-complete or permanent-partial interruption of the maternal-fetal blood flow. After 8 min of complete restriction of the blood flow in the pregnant rat at 18 days of gestation, the urinary concentration of 6-keto-prostaglandin F1 alpha (6k-PGF1 alpha, the stable prostacyclin metabolite) increased from 4.97 +/- 1.27 ng mg-1 creatinine to 8.09 +/- 2.47 ng mg-1 creatinine and 13.02 +/- 4.5 ng mg-1 creatinine after the second and third post-operative day respectively. The urinary concentration of the 2,3-dinor derivative of prostacyclin reached 12.35 +/- 5.44 ng mg-1 creatinine after the second post-operative day and was reduced to 4.71 +/- 1.94 ng mg-1 creatinine after the third post-operative day. The concentration of thromboxane B2 (TxB2, the stable thromboxane A2 metabolite) increased approximately 7-fold and 13-fold over that of the control after the second and third post-operative day respectively. The urinary concentration of the 2,3-dinor derivative of TxB2 (d-TxB2) increased from about 1.42 +/- 0.3 ng mg-1 creatinine to 4.49 +/- 0.9 ng mg-1 creatinine and 7.76 +/- 2.63 ng mg-1 creatinine under the same experimental conditions. Increases in the urinary concentrations of 6k-PGF1 alpha and d-TxB2 to 94 +/- 27.76 ng mg-1 creatinine and 12.05 +/- 2.26 ng mg-1 creatinine, respectively, were observed on the second post-operative day, after the restriction time was increased to 30 min. Permanent-partial occlusion of the maternal fetal circulation resulted in excretion of PNs in the urine to similar levels produced after transient-complete restriction. High concentrations of prostacyclin (range, 0.8 ng min-1 mg-1 wet weight) were produced in vitro by uterine preparations from restricted animals after the second post-operative day. Placenta preparations from restricted animals generally exhibited a lower ability to synthesize PNS (up to 0.006 ng min-1 mg-1 wet weight) compared with uterine tissue but produced more thromboxane than their sham counterparts. The data suggest that the uterus constitutes the main source for urinary PN excretion following short episodes of maternal-fetal blood flow interruption.