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Pathophysiology of chronic nitric oxide synthase inhibition-induced fetal growth restriction in the rat.
Hypertens Pregnancy. 2011; 30(1):28-36.HP

Abstract

OBJECTIVE

To evaluate the pathophysiology of chronic nitric oxide synthase (NOS) inhibition-induced fetal growth restriction (FGR) in the rat.

METHODS

Timed-pregnant rats received L-NAME (2.5 mg/kg/h) with or without endothelin (ET-1) receptor A (ETA) antagonist from day 14 to 21 of gestation. In separate groups, ETA antagonist and/or L-NAME were discontinued on day 18. On day 21 fetal and placental weights, and maternal and fetal plasma nitrate/nitrite (NOx) were determined.

RESULTS

L-NAME led to FGR, and decreased maternal and fetal NOx. Maternal NOx was further decreased when ETA antagonist was co-administered with L-NAME. ETA antagonism along with L-NAME did not impact fetal growth. Discontinuation of L‐NAME on day 18 resulted in normal fetal and placental growth at day 21 and an increase of maternal NOx. Simultaneous cessation of both NOS inhibition and ETA antagonism on day 18 produced FGR at day 21, whereas continuation of ETA antagonism after discontinuation of L-NAME resulted in normal fetal growth.

CONCLUSIONS

NOS inhibition in the pregnant rat leads to decreased maternal and fetal nitric oxide (NO) production and FGR. The effects of NOS inhibition on fetal growth are reversible, and are mediated at least in part by ET-1. With chronic NOS inhibition, ETA antagonism improves but does not normalize fetal growth, and may allow increased access of L-NAME to the fetal compartment. Continued access of L-NAME to the fetal compartment may limit the effect on fetal growth of any therapeutic intervention in this model of FGR.

Authors+Show Affiliations

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Evanston Northwestern Healthcare, Evanston, IL, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21265058

Citation

Neerhof, Mark G., et al. "Pathophysiology of Chronic Nitric Oxide Synthase Inhibition-induced Fetal Growth Restriction in the Rat." Hypertension in Pregnancy, vol. 30, no. 1, 2011, pp. 28-36.
Neerhof MG, Synowiec S, Khan S, et al. Pathophysiology of chronic nitric oxide synthase inhibition-induced fetal growth restriction in the rat. Hypertens Pregnancy. 2011;30(1):28-36.
Neerhof, M. G., Synowiec, S., Khan, S., & Thaete, L. G. (2011). Pathophysiology of chronic nitric oxide synthase inhibition-induced fetal growth restriction in the rat. Hypertension in Pregnancy, 30(1), 28-36.
Neerhof MG, et al. Pathophysiology of Chronic Nitric Oxide Synthase Inhibition-induced Fetal Growth Restriction in the Rat. Hypertens Pregnancy. 2011;30(1):28-36. PubMed PMID: 21265058.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pathophysiology of chronic nitric oxide synthase inhibition-induced fetal growth restriction in the rat. AU - Neerhof,Mark G, AU - Synowiec,Sylvia, AU - Khan,Saira, AU - Thaete,Larry G, PY - 2011/1/26/entrez PY - 2011/1/28/pubmed PY - 2011/5/25/medline SP - 28 EP - 36 JF - Hypertension in pregnancy JO - Hypertens Pregnancy VL - 30 IS - 1 N2 - OBJECTIVE: To evaluate the pathophysiology of chronic nitric oxide synthase (NOS) inhibition-induced fetal growth restriction (FGR) in the rat. METHODS: Timed-pregnant rats received L-NAME (2.5 mg/kg/h) with or without endothelin (ET-1) receptor A (ETA) antagonist from day 14 to 21 of gestation. In separate groups, ETA antagonist and/or L-NAME were discontinued on day 18. On day 21 fetal and placental weights, and maternal and fetal plasma nitrate/nitrite (NOx) were determined. RESULTS: L-NAME led to FGR, and decreased maternal and fetal NOx. Maternal NOx was further decreased when ETA antagonist was co-administered with L-NAME. ETA antagonism along with L-NAME did not impact fetal growth. Discontinuation of L‐NAME on day 18 resulted in normal fetal and placental growth at day 21 and an increase of maternal NOx. Simultaneous cessation of both NOS inhibition and ETA antagonism on day 18 produced FGR at day 21, whereas continuation of ETA antagonism after discontinuation of L-NAME resulted in normal fetal growth. CONCLUSIONS: NOS inhibition in the pregnant rat leads to decreased maternal and fetal nitric oxide (NO) production and FGR. The effects of NOS inhibition on fetal growth are reversible, and are mediated at least in part by ET-1. With chronic NOS inhibition, ETA antagonism improves but does not normalize fetal growth, and may allow increased access of L-NAME to the fetal compartment. Continued access of L-NAME to the fetal compartment may limit the effect on fetal growth of any therapeutic intervention in this model of FGR. SN - 1525-6065 UR - https://www.unboundmedicine.com/medline/citation/21265058/Pathophysiology_of_chronic_nitric_oxide_synthase_inhibition_induced_fetal_growth_restriction_in_the_rat_ L2 - https://www.tandfonline.com/doi/full/10.3109/10641950903322915 DB - PRIME DP - Unbound Medicine ER -