URINARY-EXCRETION OF PROSTACYCLIN IN A RAT MODEL OF UTEROPLACENTAL VASCULATURE OCCLUSION - IMPLICATIONS FOR FETAL GROWTH-RETARDATION

An experimental model was devised in the pregnant rat to study by a co mbined high pressure liquid chromatography and radioimunoassay techniq ue 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 pr egnant rat at 18 days of gestation, the urinary concentration of 6-ket o-prostaglandin F-1 alpha (6k-PGF(1 alpha), the stable prostacyclin me tabolite) 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 concent ration of the 2,3-dinor derivative of prostacyclin reached 12.35+/-5.4 4 ng mg(-1) creatinine after the second post-operative day and was red uced to 4.71+/-1.94 ng mg(-1) creatinine after the third post-operativ e day. The concentration of thromboxane B-2 (TxB(2), the stable thromb oxane A(2) metabolite) increased approximately 7-fold and 13-fold over that of the control after the second and third post-operative day res pectively. The urinary concentration of the 2,3-dinor derivative of Tx B(2) (d-TxB(2)) increased from about 1.42+/-0.3 ng mg(-1) creatinine t o 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 conc entrations of 6k-PGF(1 alpha) and d-TxB(2) to 94+/-27.76 ng mg(-1) cre atinine and 12.05+/-2.26 ng mg(-1) creatinine, respectively, were obse rved 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 leve ls produced after transient-complete restriction. High concentrations of prostacyclin (range, 0.8 ng min(-1) mg(-1) wet weight) were produce d in vitro by uterine preparations from restricted animals after the s econd post-operative day. Placenta preparations from restricted animal s generally exhibited a lower ability to synthesize PNs (up to 0.006 n g 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 follow ing short episodes of maternal-fetal blood flow interruption.