The Role of Endothelin-1 and Oxidative Stress In Pregnancy Induced Hypertension

Pregnancy Induced Hypertension  PIH  is one of the most frequent complications of pregnancy , however little is known about its etiology. Endothelial dysfunction serves as a causative factor in the initiation of the maternal pathophysiological changes of PIH & is not just a result of this disorder. Endothelin-1 may play an important role in the pathophysiology of PIH, either by acting on vascular smooth muscle directly to induce contraction or by increasing the formation of angiotensin II. Pregnancy induced hypertension is associated with endothelial dysfunction & could be caused by oxidative stress. Recent evidence suggest the role of oxidative stress in PIH. The high level of malondiahyde  MDA  may reflect the excessive oxidative damage in PIH. The study sample consist of 50 normal non pregnant women, 50 normotensive pregnant women, and 50 preeclamptic pregnant women in their third trimester in Mosul city. The aim of this study was designed to evaluate the role of endothelial dysfunction and oxidative stress in pathogenesis of PIH. The results of this study showed that there was a highly significant elevation (P  0.000) in the serum level of endothelin-1 in the preeclamptic pregnant women in comparison with normotensive pregnant & the control group. Also there was a highly significant elevation (P  0.000) in the level of serum MDA in the preeclamptic pregnant women in comparison with normotensive pregnancy & the control group. The serum endothelin-1 has a significant negative correlation with both maternal age

Endothelial changes also appear to involve a relative deficiency in the production of Nitric oxide, a vasodilator and inhibitor of platelets aggregation ,along with increased production of endothelin-1.9.Endothelin 1-was discovered 28 years ago ( in 1998).Because it is one of the most potent vasoconstrictor in vivo, a pathophysiological role for this peptide as a mediators of the hypertension has been postulated.10).Endothelin-1 may play an important role in the pathophysiology of PIH, either by acting on vascular smooth muscle directly to induce contraction or by increasing the formation of angiotensin II, to which there is an increased vasopresser response in PIH.(11).Many studies up to now have demonstrated elevated plasma Endothelin-1 levels in PIH.12.Recent evidence suggest the role of oxidative stress in PIH as it associated with lipid changes , and an increase in the lipid peroxidation ,both in the placenta and systemically, suggested that oxidative stress (an imbalanced between free radical synthesis and antioxidant defense )may be involved in the endothelial cell dysfunction.Malondiahyde MDA is the end product of lipid peroxidation & reflects the oxidative status of the biological system.13, the high level of MDA may reflect the excessive oxidative damage in PIH.(14).

Subjects and Methods
This study represents a case control study, and it was conducted during the period from March 2011 to March 2012 in al-Batool and al-Khansaa teaching hospitals.The subjects involved in this study were divided into three groups: Group1 which served as a control group included 50 apparently healthy, non-pregnant, normotensive women, their ages ranged from (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) years.Group2 which composed of 50 normotensive apparantly healthy pregnant women in their third trimester, their ages ranged from   College and Hospital approved the study protocol and a verbal consent was obtained from the controls and the patients before the collection of the blood samples.About 5ml of fasting venous blood samples were obtained for the measurement of the biochemical parameters from all subjects included in this study by anticubital venepuncture and using disposable plastic syringe, without using elastic band tourniquet.The blood was allowed to clot and the serum was obtained by centrifugation at 3000rpm for 10 minutes.The serum was used to measure serum endothelin-1 (ET-1) concentration was determined by enzyme immunoassay (EIA), by using a kit supplied from (Enzo life sciences), and serum malondialdehyde (MDA) concentration was determined by method of Buege and Aust (1987).15.

Statistical Analysis
The SPSS statistical package version 19 was used for the statistic analysis of the data.The comparison between the studied groups were done by ANOVAone way analysis of variance followed by Duncan's multiple range test  DMRT.Pearson correlation was used to find the relation between the studied parameters.The statistical test results were considered highly significant at P ≤ 0.001, significant at p ≤ 0.05, and not significant at p ≤ 0.05.

Results
Table

Discussion
Generalized maternal endothelial cell dysfunction may explain the multisystemic nature of preeclampsia.Pregnancy induced hypertension is accompanied by elevated endothelin-1 level with even higher levels in patients with severe PIH or HELLP syndrome11.The present study showed a significant elevation in serum level of endothelin-1ET-1in the preeclamptic women as compared to the control group and normotensive pregnant women at p 0.000.This elevation of serum endothelin-1 in preeclamptic women may support the idea that ET-1 may play an important role in the pathophysiology of preeclampsia, either by acting on vascular smooth muscle directly to induce vasoconstriction or by increase angiotensin II to which there is an increased vasopresser response in preeclampsia.(11).