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Chronic blockade of nitric oxide-synthase and endothelin receptors during pregnancy in the rat: effect on pregnancy outcome.
J Soc Gynecol Investig. 1998 May-Jun; 5(3):132-9.JS

Abstract

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-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), the ETA-/ETB-receptor antagonist bosentan (Roche Basel, Switzerland) or both, or received no treatment (controls). Blood pressure, body weight, and drug intake were measured at regular intervals. Pregnancy outcome and proteinurea were also determined. Analysis of variance and paired Student t test were used for statistical analysis.

RESULTS

Chronic L-NAME treatment increased systolic blood pressure by 69 and 64 mmHg in pregnant and virgin rats respectively (P < .05). Bosentan-blunted, L-NAME-induced hypertension at the beginning (P < .05), but not at the end of the treatment period in all rats examined. N omega-nitro-L-arginine methyl 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 both effects failed to reach statistical significance.

CONCLUSIONS

The effects of chronic, NO-synthase-blockade on blood pressure in gravid rats can be reversed only temporarily by ETA-/ETB-antagonism, suggesting an involvement of endothelin-1 in the early phase of the L-NAME-induced, preeclampsia-like syndrome during pregnancy, although at later stages other mechanisms may come into play.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, University Hospital Zürich, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9614642

Citation

Wight, E, et al. "Chronic Blockade of Nitric Oxide-synthase and Endothelin Receptors During Pregnancy in the Rat: Effect On Pregnancy Outcome." Journal of the Society for Gynecologic Investigation, vol. 5, no. 3, 1998, pp. 132-9.
Wight E, Küng CF, Moreau P, et al. Chronic blockade of nitric oxide-synthase and endothelin receptors during pregnancy in the rat: effect on pregnancy outcome. J Soc Gynecol Investig. 1998;5(3):132-9.
Wight, E., Küng, C. F., Moreau, P., Takase, H., & Lüscher, T. F. (1998). Chronic blockade of nitric oxide-synthase and endothelin receptors during pregnancy in the rat: effect on pregnancy outcome. Journal of the Society for Gynecologic Investigation, 5(3), 132-9.
Wight E, et al. Chronic Blockade of Nitric Oxide-synthase and Endothelin Receptors During Pregnancy in the Rat: Effect On Pregnancy Outcome. J Soc Gynecol Investig. 1998 May-Jun;5(3):132-9. PubMed PMID: 9614642.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic blockade of nitric oxide-synthase and endothelin receptors during pregnancy in the rat: effect on pregnancy outcome. AU - Wight,E, AU - Küng,C F, AU - Moreau,P, AU - Takase,H, AU - Lüscher,T F, PY - 1998/6/6/pubmed PY - 1998/6/6/medline PY - 1998/6/6/entrez SP - 132 EP - 9 JF - Journal of the Society for Gynecologic Investigation JO - J Soc Gynecol Investig VL - 5 IS - 3 N2 - 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-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), the ETA-/ETB-receptor antagonist bosentan (Roche Basel, Switzerland) or both, or received no treatment (controls). Blood pressure, body weight, and drug intake were measured at regular intervals. Pregnancy outcome and proteinurea were also determined. Analysis of variance and paired Student t test were used for statistical analysis. RESULTS: Chronic L-NAME treatment increased systolic blood pressure by 69 and 64 mmHg in pregnant and virgin rats respectively (P < .05). Bosentan-blunted, L-NAME-induced hypertension at the beginning (P < .05), but not at the end of the treatment period in all rats examined. N omega-nitro-L-arginine methyl 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 both effects failed to reach statistical significance. CONCLUSIONS: The effects of chronic, NO-synthase-blockade on blood pressure in gravid rats can be reversed only temporarily by ETA-/ETB-antagonism, suggesting an involvement of endothelin-1 in the early phase of the L-NAME-induced, preeclampsia-like syndrome during pregnancy, although at later stages other mechanisms may come into play. SN - 1071-5576 UR - https://www.unboundmedicine.com/medline/citation/9614642/Chronic_blockade_of_nitric_oxide_synthase_and_endothelin_receptors_during_pregnancy_in_the_rat:_effect_on_pregnancy_outcome_ L2 - https://medlineplus.gov/bloodpressuremedicines.html DB - PRIME DP - Unbound Medicine ER -