The effect of indomethacin and prostacyclin agonists on blood pressure in a rat model of preeclampsia

OBJECTIVE: This study was designed to determine the effects of cyclooxygena se inhibition and prostacyclin agonists on the hypertension induced by nitr ic oxide synthase blockade in a previously characterized rat model of preec lampsia. STUDY DESIGN: A condition similar to preeclampsia was induced by infusing p regnant rats with the nitric oxide synthase inhibitor N-G-nitro-L-arginine methyl ester through subcutaneously implanted osmotic minipumps. Blood pres sure was measured with the tail cuff method. In the first experiment the ra ts received either vehicle alone (control group), N-G-nitro-L-arginine meth yl ester (50 mg/d), indomethacin (0.1 mg/d), or N-G-nitro-L-arginine methyl ester plus indomethacin beginning on day 17 of pregnancy. In the second ex periment the rats received vehicle alone (control group), N-G-nitro-L-argin ine methyl ester (50 mg/d), or N-G-nitro-L-arginine methyl ester plus ilopr ost (31 mu g/d). In a third experiment cicaprost(15 mu g/d) was substituted for iloprost. RESULTS: Except for an increase on the day after insertion of the pump indo methacin had no significant effect on the hypertension induced by N-G-nitro -L-arginine methyl ester. Both prostacyclin agonists (iloprost and cicapros t), however, attenuated the rise in blood pressure usually seen after N-G-n itro-L-arginine methyl ester administration. CONCLUSIONS: Nonselective inhibition of the cyclooxygenase enzymatic system does not influence the hypertension seen in the rat preeclampsia model ind uced by chronic nitric oxide deficiency. The hypertension in this model can be partially reversed with prostacyclin analogs. (Am J Obstet Gynecol 1999 ;180:1191-5.).