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The quantification of nitric oxide production in pregnant and non-pregnant women

The quantification of nitric oxide production in pregnant and non-pregnant women
The quantification of nitric oxide production in pregnant and non-pregnant women

Nitric oxide (NO) is synthesised from L-arginine by the enzyme nitric oxide synthase (NOS). The role which NO plays in human pregnancy has not yet been widely explored, in part due to the difficulties of quantification in vivo. For this thesis I developed assays locally to allow indirect quantification of NO production in vivo in two ways: measuring NOS activity in tissue samples and measuring nitrite/nitrate levels in plasma samples. These techniques were then used, in conjunction with colour Doppler ultrasound, to explore the gestation related variations in NO production in 50 normal pregnancies in a cross-sectional study. Subsequently the study was extended to include some pregnancies complicated by abnormal Dopplers or fetal growth retardation. I also investigated the effect of NO donor drugs on utero-placental blood flow in early pregnancy and the effect of exogenous oestrogen on NO production in non-pregnant women. The main findings of the research were:-

1. Plasma nitrate levels rose in the second and third trimesters of pregnancy implying a systemic increase in NO production at that time.

2. Trophoblast NOS activity was highest in the first trimester of pregnancy and fell steadily towards term in normal pregnancies suggesting that trophoblast NO may play a significant role in the implantation process.

3. In pregnancies complicated by IUGR, trophoblast NOS activity was very low when compared to normals, supporting the idea of a relative NO deficiency in such pregnancies.

4. NO donor drugs increased utero-placental diastolic blood flow in normal early pregnancy whereas prostacyclin did not, implying that NO plays a specific role in controlling local uteroplacental vascular tone.

5. Exogenous oestrogen increased plasma nitrate levels in women of child bearing age in a placebo controlled study, suggesting that NO is one of the mediators through which oestrogen exerts its cardiovascular effects.

University of Southampton
Ramsay, Bruce
2270da5e-6f2e-4871-8b26-5f2e891e963e
Ramsay, Bruce
2270da5e-6f2e-4871-8b26-5f2e891e963e

Ramsay, Bruce (1997) The quantification of nitric oxide production in pregnant and non-pregnant women. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

Nitric oxide (NO) is synthesised from L-arginine by the enzyme nitric oxide synthase (NOS). The role which NO plays in human pregnancy has not yet been widely explored, in part due to the difficulties of quantification in vivo. For this thesis I developed assays locally to allow indirect quantification of NO production in vivo in two ways: measuring NOS activity in tissue samples and measuring nitrite/nitrate levels in plasma samples. These techniques were then used, in conjunction with colour Doppler ultrasound, to explore the gestation related variations in NO production in 50 normal pregnancies in a cross-sectional study. Subsequently the study was extended to include some pregnancies complicated by abnormal Dopplers or fetal growth retardation. I also investigated the effect of NO donor drugs on utero-placental blood flow in early pregnancy and the effect of exogenous oestrogen on NO production in non-pregnant women. The main findings of the research were:-

1. Plasma nitrate levels rose in the second and third trimesters of pregnancy implying a systemic increase in NO production at that time.

2. Trophoblast NOS activity was highest in the first trimester of pregnancy and fell steadily towards term in normal pregnancies suggesting that trophoblast NO may play a significant role in the implantation process.

3. In pregnancies complicated by IUGR, trophoblast NOS activity was very low when compared to normals, supporting the idea of a relative NO deficiency in such pregnancies.

4. NO donor drugs increased utero-placental diastolic blood flow in normal early pregnancy whereas prostacyclin did not, implying that NO plays a specific role in controlling local uteroplacental vascular tone.

5. Exogenous oestrogen increased plasma nitrate levels in women of child bearing age in a placebo controlled study, suggesting that NO is one of the mediators through which oestrogen exerts its cardiovascular effects.

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Published date: 1997

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Local EPrints ID: 463135
URI: http://eprints.soton.ac.uk/id/eprint/463135
PURE UUID: a7c9e101-b8c0-46e1-b294-7cd937b3c80d

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Date deposited: 04 Jul 2022 20:45
Last modified: 16 Mar 2024 19:02

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Author: Bruce Ramsay

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