The effect of an endothelin antagonist on blood pressure in a rat model of preeclampsia

OBJECTIVE: To determine the role of endothelin (ET) in a previously characterized animal model of preeclampsia by studying the effect of a specific ET antagonist, BQ123, on blood pressure (BP). STUDY DESIGN: As previously reported, a preeclampsia-like condition was induced by infusing pregnant rats with the nitric oxide synthase inhibitor, L-NAME. Osmotic minipumps were inserted subcutaneously into timed pregnant Harlan-Sprague-Dawley rats on day 17 of pregnancy (term 22 days). The pumps were loaded to continuously deliver either vehicle (Control group), L-NAME 50 mg/d alone (L-NAME group) or with BQ 0.5 mg/d (L-NAME + BQ/0.5 group). In a similar, but separate experiment, the dose of BQ was increased to 1 mg/d (L-NAME + BQ/1 group). BP was measured with the tailcuff method before pump insertion and daily until postpartum day 2. Data presented as mean ±SE. RESULTS: Except for a decrease on the day following pump insertion, BQ/0.5 had no significant effect on the hypertension induced by L-NAME (Fig. A). At the higher dose however, BQ 123 significantly attenuated the increase in blood pressure induced by L-NAME during most of the study period (Fig. B). CONCLUSION: Endothelin appears to play a role in the hypertension described with the preeclampsia-like condition induced by nitric oxide deficiency in the rat.