The role of endogenous endothelin in the regulation of uteroplacental and renal blood flow during pregnancy in conscious rats.
Advancing pregnancy is characterized by a ten-fold increase in uterine blood flow and a 50 per cent increase in renal blood flow. To evaluate the involvement of endogenous endothelin (ET) in these haemodynamic changes the effect of bosentan, an ETA/B receptor antagonist, on uteroplacental and renal blood flow was studied in awake pregnant Sprague-Dawley rats. Regional blood flows were measured using microsphere technique immediately prior to and 30 min after bosentan administration (20 mg/kg i.v.). Four groups of animals (term: 23 days) were included: bosentan was administered to ten rats at gestation day (GD) 19 and nine at GD 20-21. In addition, four rats at GD 19 and five animals at GD 20-21 received saline and served as control groups. Basal placental blood flow increased significantly from 19 days' gestation to 20-21 days. Basal myometrial blood flow did not change with gestational age. At gestation day 19 bosentan increased placental and myometrial blood flow significantly (80 per cent and 43 per cent, respectively, P<0.05). This effect was not observed at gestation days 20-21. Renal blood flow did not change in response to bosentan at GD 19 but decreased by 20 per cent at GD 20-21 (P<0.01). In conclusion, in the awake pregnant rat there is a significant endogenous ET dependent vasoconstrictor tone in the uteroplacental vessels that diminishes towards term. We speculate that this change in responsiveness to endogenous ET contribute to the increase in placental blood flow in late gestation.