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

Gayle L. Olson, George R. Saade, Irina Buhimschi, Kristof Chwalisz, Robert E. Garfield

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

OBJECTIVE: We attempted to determine the role of endothelin in a previously characterized animal model of preeclampsia by studying the effect of a specific endothelin antagonist, BQ123, on blood pressure. STUDY DESIGN: A preeclampsia-like condition was induced by infusing pregnant rats with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester. 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) 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 to 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 mg/d had no significant effect on the hypertension induced by N(G)-nitro-L-arginine methyl ester. At the higher dose, however, BQ123 significantly attenuated 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 attenuated by the use of an endothelin antagonist, thereby supporting the role of endothelin in the hypertension described with the preeclampsia-like condition seen in pregnant rats.

Original languageEnglish (US)
Pages (from-to)638-641
Number of pages4
JournalAmerican journal of obstetrics and gynecology
Volume181
Issue number3
DOIs
StatePublished - 1999

Keywords

  • Endothelin
  • Nitric oxide inhibition
  • Preeclampsia

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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