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 cyclooxygenase inhibition and prostacyclin agonists on the hypertension induced by nitric oxide synthase blockade in a previously characterized rat model of preeclampsia. STUDY DESIGN: A condition similar to preeclampsia was induced by infusing pregnant rats with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester through subcutaneously implanted osmotic minipumps. Blood pressure was measured with the tail cuff method. In the first experiment the rats received either vehicle alone (control group), N(G)-nitro-L-arginine methyl 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 experiment the rats received vehicle alone (control group), N(G)-nitro-L-arginine methyl ester (50 mg/d), or N(G)-nitro-L- arginine methyl ester plus iloprost (31 μg/d). In a third experiment cicaprost (15 μg/d) was substituted for iloprost. RESULTS: Except for an increase on the day after insertion of the pump indomethacin had no significant effect on the hypertension induced by N(G)-nitro-L-arginine methyl ester. Both prostacyclin agonists (iloprost and cicaprost), however, attenuated the rise in blood pressure usually seen after N(G)-nitro-L- arginine methyl ester administration. CONCLUSIONS: Nonselective inhibition of the cyclooxygenase enzymatic system does not influence the hypertension seen in the rat preeclampsia model induced by chronic nitric oxide deficiency. The hypertension in this model can be partially reversed with prostacyclin analogs.