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

OBJECTIVE: We attempted to determine the role of endothelin in a previously characterized animal model of preeclampsia by studying the effect of a spe cific endothelin antagonist, BQ123, on blood pressure. STUDY DESIGN: A preeclampsia-like condition was induced by infusing pregnan t rats with the nitric oxide synthase inhibitor Nc-nitro-L-arginine methyl ester. Osmotic minipumps were inserted subcutaneously into timed pregnant H arlan-Sprague-Dawley rats on day 17 of pregnancy (term, 22 days). The pumps were loaded to continuously deliver either vehicle (control group) or N-G- nitro-L-arginine methyl ester 50 mg/d, either alone or with BQ123 at 0.5 mg /d. In a similar but separate experiment, the dose of BQ123 was increased t o 1 mg/d. Blood pressure was measured with the tail-cuff method before pump insertion and then daily until postpartum day 2. RESULTS: Except for a decrease on the day after pump insertion, BQ123 0.5 m g/d had no significant effect on the hypertension induced by N-G-nitro-L-ar ginine methyl ester. At the higher dose, however, BQ123 significantly atten uated the increase in blood pressure induced by N-G-nitro-L-arginine methyl ester during most of the study period. CONCLUSION: The effect of nitric oxide inhibition can be successfully atten uated by the use of an endothelin antagonist, thereby supporting the role o f endothelin in the hypertension described with the preeclampsia-like condi tion seen in pregnant rats.