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Long-term nitric oxide blockade in the pregnant rat: effects on blood pressure and plasma levels of endothelin-1.
Am J Obstet Gynecol. 1996 Aug; 175(2):484-8.AJ

Abstract

OBJECTIVE

Abnormalities in the production of nitric oxide and endothelin-1 have been implicated in the development of preeclampsia. We postulated that long-term nitric oxide synthase inhibition with L-nitro-arginine methyl ester would induce sustained hypertension, a rise in plasma levels of endothelin-1, and fetal growth restriction.

STUDY DESIGN

Conscious virgin and pregnant Sprague-Dawley rats received infusions of vehicle or L-nitro-arginine methyl ester (2.5 mg/kg/hr) for 11 days. Mean arterial pressure was assessed serially. On day 21 of gestation (or equivalent in virgin rats) plasma was collected for endothelin-1 levels; pup weight and litter size were determined. Data were analyzed with analysis of variance and regression techniques.

RESULTS

Mean arterial pressure was constant in virgin control rats (n = 7) but declined in pregnant control rats (n = 11) as gestation advanced. Nitric oxide synthase inhibition in virgin (n = 10) and pregnant (n = 11) rats caused sustained elevations in mean arterial pressure (165 +/- 7 vs 100 +/- 3 mm Hg, L-nitro-arginine methyl ester vs control virgin rats, p < 0.0001; 149 +/- 5 vs 91 +/- 2 mm Hg, L-nitro-arginine methyl ester vs control pregnant rats, p < 0.0001). L-nitro-arginine methyl ester induced a rise in plasma endothelin-1 levels in virgin (4.4 +/- 0.1 vs 3.5 +/- 0.1 pg/ml, L-nitro-arginine methyl ester vs control, p < 0.0001) and pregnant rats (3.0 +/- 0.1 vs 2.6 +/- 0.1 pg/ml, L-nitro-arginine methyl ester vs control, p < 0.0001). Pregnant rats had lower endothelin-1 levels than did virgin rats (p < 0.0001). Mean arterial pressure and endothelin-1 were significantly correlated in pregnant rats. L-nitro-arginine methyl ester decreased pup weight (2.4 +/- 0.4 vs 3.7 +/- 0.2 gm/pup/litter, L-nitro-arginine methyl ester vs control, p < 0.01) and litter size (6.6 +/- 1.3 vs 10.2 +/- 0.9 pups/litter, L-nitro-arginine methyl ester vs control, p < 0.05).

CONCLUSIONS

Long-term nitric oxide synthase blockade causes sustained hypertension, elevated levels of endothelin-1, and fetal growth restriction. Although the endocrine and pressor effects are not unique to pregnancy, this model clearly induces some of the changes seen in preeclampsia and may be useful for studying specific interventions.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center Burns and Allen Research Institute, Los Angeles, California, USA.No 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

8765273

Citation

Edwards, D L., et al. "Long-term Nitric Oxide Blockade in the Pregnant Rat: Effects On Blood Pressure and Plasma Levels of Endothelin-1." American Journal of Obstetrics and Gynecology, vol. 175, no. 2, 1996, pp. 484-8.
Edwards DL, Arora CP, Bui DT, et al. Long-term nitric oxide blockade in the pregnant rat: effects on blood pressure and plasma levels of endothelin-1. Am J Obstet Gynecol. 1996;175(2):484-8.
Edwards, D. L., Arora, C. P., Bui, D. T., & Castro, L. C. (1996). Long-term nitric oxide blockade in the pregnant rat: effects on blood pressure and plasma levels of endothelin-1. American Journal of Obstetrics and Gynecology, 175(2), 484-8.
Edwards DL, et al. Long-term Nitric Oxide Blockade in the Pregnant Rat: Effects On Blood Pressure and Plasma Levels of Endothelin-1. Am J Obstet Gynecol. 1996;175(2):484-8. PubMed PMID: 8765273.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term nitric oxide blockade in the pregnant rat: effects on blood pressure and plasma levels of endothelin-1. AU - Edwards,D L, AU - Arora,C P, AU - Bui,D T, AU - Castro,L C, PY - 1996/8/1/pubmed PY - 1996/8/1/medline PY - 1996/8/1/entrez SP - 484 EP - 8 JF - American journal of obstetrics and gynecology JO - Am J Obstet Gynecol VL - 175 IS - 2 N2 - OBJECTIVE: Abnormalities in the production of nitric oxide and endothelin-1 have been implicated in the development of preeclampsia. We postulated that long-term nitric oxide synthase inhibition with L-nitro-arginine methyl ester would induce sustained hypertension, a rise in plasma levels of endothelin-1, and fetal growth restriction. STUDY DESIGN: Conscious virgin and pregnant Sprague-Dawley rats received infusions of vehicle or L-nitro-arginine methyl ester (2.5 mg/kg/hr) for 11 days. Mean arterial pressure was assessed serially. On day 21 of gestation (or equivalent in virgin rats) plasma was collected for endothelin-1 levels; pup weight and litter size were determined. Data were analyzed with analysis of variance and regression techniques. RESULTS: Mean arterial pressure was constant in virgin control rats (n = 7) but declined in pregnant control rats (n = 11) as gestation advanced. Nitric oxide synthase inhibition in virgin (n = 10) and pregnant (n = 11) rats caused sustained elevations in mean arterial pressure (165 +/- 7 vs 100 +/- 3 mm Hg, L-nitro-arginine methyl ester vs control virgin rats, p < 0.0001; 149 +/- 5 vs 91 +/- 2 mm Hg, L-nitro-arginine methyl ester vs control pregnant rats, p < 0.0001). L-nitro-arginine methyl ester induced a rise in plasma endothelin-1 levels in virgin (4.4 +/- 0.1 vs 3.5 +/- 0.1 pg/ml, L-nitro-arginine methyl ester vs control, p < 0.0001) and pregnant rats (3.0 +/- 0.1 vs 2.6 +/- 0.1 pg/ml, L-nitro-arginine methyl ester vs control, p < 0.0001). Pregnant rats had lower endothelin-1 levels than did virgin rats (p < 0.0001). Mean arterial pressure and endothelin-1 were significantly correlated in pregnant rats. L-nitro-arginine methyl ester decreased pup weight (2.4 +/- 0.4 vs 3.7 +/- 0.2 gm/pup/litter, L-nitro-arginine methyl ester vs control, p < 0.01) and litter size (6.6 +/- 1.3 vs 10.2 +/- 0.9 pups/litter, L-nitro-arginine methyl ester vs control, p < 0.05). CONCLUSIONS: Long-term nitric oxide synthase blockade causes sustained hypertension, elevated levels of endothelin-1, and fetal growth restriction. Although the endocrine and pressor effects are not unique to pregnancy, this model clearly induces some of the changes seen in preeclampsia and may be useful for studying specific interventions. SN - 0002-9378 UR - https://www.unboundmedicine.com/medline/citation/8765273/Long_term_nitric_oxide_blockade_in_the_pregnant_rat:_effects_on_blood_pressure_and_plasma_levels_of_endothelin_1_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9378(96)70166-7 DB - PRIME DP - Unbound Medicine ER -