Antioxidant systems in normal pregnancy and in pregnancy-induced hypertension Stephen]. Wisdom, MB, ChB,. Rhoda Wilson, PhD; James H. McKillop, PhD; and JamesJ. Walker, MB, ChB" Glasgow, Scotland Increased free radical activity has been implicated in the pathogenesis of pregnancy-induced hypertension. This article investigates whether changes in antioxidant systems contribute to this condition. Two extracellular (plasma thiols and ceruloplasmin) and two intracellular (red blood cell lysate thiols and red blood cell superoxide dismutase) antioxidant markers were assayed in 25 nonpregnant women, 16 pregnant women with normal blood pressure, 19 women with pregnancy-induced hypertension, and 13 women with proteinuric pregnancy-induced hypertension. In the normotensive pregnant group (in comparison with the nonpregnant group) the plasma thiol level was reduced (p < 0.001) and the ceruloplasmin level raised (p < 0.005), suggesting increased free radical activity. The lysate thiol level increased (p < 0.005), which may reflect a compensatory protective response. In the hypertensive pregnant groups the lysate thiol rise was not present. These red blood cells may be more prone to oxidative stress. Whether this situation is a cause or an effect of oxidative stress in pregnancy-induced hypertension has yet to be elucidated. (AM J OBSTET GVNECOL 1991 ;165:1701-4.)

Key words: Antioxidants, free radicals, pregnancy-induced hypertension

Damage from free radicals has been implicated in many pathologic conditions.! It is envisaged that increased free radical activity (oxidative stress) arises from increased production of free radicals or a deficiency in the protective antioxidant systems. Pregnancyinduced hypertension is associated with endothelial cell dysfunction." Such dysfunction could be caused by oxidative stress: the unsaturated lipids and thiol-containing proteins in cell membranes are susceptible to free radical attack. 3 There is evidence of increased free radical activity in pregnancy-induced hypertension 4 . 5 but little is known about the part played by changes in specific antioxidants. In this study two extracellular (plasma thiols and ceruloplasmin) and two intracellular (red blood cell lysate thiols and red blood cell superoxide dismutase) components of antioxidant systems have been assessed to reflect the oxidative stress across the cell membrane. Thiol groups are involved in the defense against oxidative stress. 6 Oxidative stress will result in the conversion of thiol groups to disulfide forms, with a consequent fall in the observed thiol level. Plasma thiols are a heterogeneous group offering a nonspecific buffer to oxidative stress. Red blood cell lysate thiols

From the Departments of Obstetrics and Gynaecology" and Medicine,' University of Glasgow. Presented in part at the Thirty-eighth Annual Meeting of the Society for Gynecologic Investigation, San Antonio, Texas, March 20-23,

1991.

Reprint requests: Stephen]. Wisdom, Glasgow Royal Maternity Hospital, Rottenrow, Glasgow, Scotland G4 DNA.

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consist mainly of glutathione, which has a specific antioxidant role. The exact mechanism for the antioxidant ability of ceruloplasmin is uncertain. It may function by converting Fe 2 + to Fe3+, Fe 2 + being an autooxidation catalyst. 7 Superoxide dismutase specifically detoxifies the superoxide anion radical. Because ceruloplasmin and superoxide dismutase have enzymic roles, they are not consumed by oxidative stress. Their levels, however, indicate the capacity to withstand oxidative stress and teleologically would be expected to be elevated in response to oxidative stress. The effects of pregnancy and pregnancy-induced hypertension on these four antioxidant parameters were investigated.

Material and methods There were four study groups: healthy, nonpregnant women in the reproductive era (n = 25); pregnant women with normal blood pressure (n = 16); women with pregnancy-induced hypertension without proteinuria (n = 19); and women with pregnancy-induced hypertension with proteinuria (n = 13). All pregnant women were primigravid and in the third trimester. Pregnancy-induced hypertension was defined as a persistent or recurrent diastolic blood pressure of 2:90 mm Hg developing during pregnancy at >20 weeks' gestation, and resolving :56 weeks post partum. Proteinuria was defined as the persistent presence of protein in the urine of 2: + on urine "dipstick" testing or >300 mg of protein excreted in 24 hours (this measurement was preferred where available). 17()1

1702 Wisdom et al.

December 1991 Am J Obstet Gynecol

Table I. Antioxidant levels in normotensive pregnant and pregnancy-induced hypertension groups compared with nonpregnant control group

Plasma thiols (U IL) Ceruloplasmin (mgllOO ml) Lysate thiols (U IL) Superoxide dis mutase (fLg/ml)

Normotensive pregnant

Nonpregnant (mean ± SD)

Mean ± SD

466 ± 59 19 ± 11 288 ± 112 62 ± 29

I

PIH without proteinuria

P Value

Mean ± SD

292 ± 85 29 ± 10

Antioxidant systems in normal pregnancy and in pregnancy-induced hypertension.

Increased free radical activity has been implicated in the pathogenesis of pregnancy-induced hypertension. This article investigates whether changes i...
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