Enhanced thromboxane synthesis during chronic reductions in uterine perfusion pressure in pregnant rats

The purpose of this study was to determine the role of thromboxane A 2 (TXA 2) in a conscious, chronically instrumented rat model of pregnancy-induced hypertension (PIH) produced by chronic reductions in uterine perfusion pressure (RUPP). Mean arterial pressure (MAP), glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and 24-h urinary excretion of TXB 2 (metabolite of TXA 2) were determined in normal pregnant rats and RUPP pregnant rats. At day 20 of pregnancy, RUPP rats showed a significantly ( P < .05) higher MAP (125 ± 3 mm Hg v 100 ± 2 mm Hg) as compared with normal pregnant controls. The elevation in arterial pressure in RUPP group was associated with a marked increase ( P < .05) in the urinary concentration of TXB 2 compared with normal pregnant group (3663 ± 488 v 2646 ± 257 pg/24 h). Baseline GFR (1.74 ± 0.13 v 2.40 ± 0.20 mL/min, respectively, P < .05) and ERPF (5.13 ± 0.44 v 6.44 ± 0.58 mL/min, respectively) were decreased in RUPP rats relative to pregnant controls. Infusion of a TX receptor antagonist, SQ 29,548 (2 mg/kg bolus plus 2 mg/kg per h infusion) had no significant effect on increased MAP in RUPP pregnant rats. Similarly, ERPF and GFR did not change during acute blockade of TXA 2 receptors in this group. These findings suggest that enhanced production of TXA 2 does not play a major role in mediating the hypertension and renal vasoconstriction produced by chronic RUPP in pregnant rats.