CHRONIC BLOCKADE OF NITRIC-OXIDE SYNTHASE AND ENDOTHELIN RECEPTORS DURING PREGNANCY IN THE RAT - EFFECT ON PREGNANCY OUTCOME

OBJECTIVES: To investigate the effects of endothelin-1 (ET-1) receptor antagonism and/or chronic blockade of nitric oxide (NO) production on pregnancy outcome in the rat. METHODS: Pregnant or nonpregnant Wistar rats were either treated orally for up to 18 days with the NO-synthas e inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME), the ETA-/E TB-receptor antagonist bosentan (Roche Basel, Switzerland) or both, or received no treatment (controls). Blood pressure, body weight, and dr ug intake were measured at regular intervals. Pregnancy outcome and pr oteinurea were also determined. Analysis of variance and paired Studen t t test were used for statistical analysis. RESULTS: Chronic L-NAME t reatment increased systolic blood pressure by 69 and 64 mmHg in pregna nt and virgin rats respectively (P < .05). Bosentan-blunted, L-NAME-in duced hypertension at the beginning (P < .05), but not at the end of t he treatment period in all rats examined. N-omega-nitro-L-arginine met hyl ester-treatment in pregnancy reduced the number of living fetuses at term (P < .05) and caused proteinurea (P < .05). Bosentan tended to reverse the effects of L-NAME on fetus number and proteinurea, but bo th effects failed to reach statistical significance. CONCLUSIONS: The effects of chronic NO-synthase-blockade on blood pressure in gravid ra ts can be reversed only temporarily by ETA-/ETB-antogonism, suggesting an involvement of endothelin-1 in the early phase of the L-NAME-induc ed, preeclampsia-like syndrome during pregnancy, although at later sta ges other mechanisms may come into play. Copyright (C) 1998 by the Soc iety for Gynecologic Investigation.