THE ROLE OF SEX HORMONES, NITRIC OXIDE AND MINERAL HOMEOSTASIS IN PREECLAMPSIA

number: 
2151
إنجليزية
Degree: 
Imprint: 
Medicine
Author: 
Faisal Ghazi Jasim
Supervisor: 
Dr. Maha Al-Bayati
Dr. Tarik Hovthy Al-Khayat
year: 
2008

Abstract:

Preeclampsia is a form of high blood pressure manifested during pregnancy, it is a common major complication causing significant morbidity and mortality; however, its etiology is unknown. The systemic vasculature is a target tissue for sex steroid hormones. Estrogen, androgen, and progesterone all influence the function and pathophysiology of the systemic circulation by influencing endothelial derived nitric-oxide pathway. Evidence suggests that sex steroids also modulate electrolyte homeostasis, but data on cation pattern during pregnancy are conflicting. Moreover, the status of ionized calcium and magnesium during pregnancy and its complication preeclampsia, and its relation with endothelial derived nitric-oxide and sex hormones have not been described adequately. The aim of this study is to demonstrate the pattern of sex steroids, minerals and electrolytes during preeclampsia with respect to normal pregnancy, and the correlation of the above parameters with nitric-oxide pathway. The present study is a cross-sectional case-control study includes measurement of nitric oxide, nitric oxide synthase, sex steroids (testosterone, progesterone, and estrogen), electrolytes (sodium and potassium), minerals (calcium and magnesium) and urinary protein in 60 patients with preeclampsia. They are classified into two groups according to gestational age: o Preeclamptics in the second trimester G1: (n=30). o Preeclamptics in the third trimester G2: (n=30,).
The results are compared with 60 apparently healthy pregnants controls. They are classified according to gestational age into two groups: o Pregnants in the second trimester G3: (n=30). o Pregnants in the third trimester G4: (n=30). The results show significant reduction in serum NO and NOS in the preeclamptics as compared to the control accompanied by a significant increase in serum testosterone; however, no significant difference in serum progesterone and serum estradiol was found between preeclamptic and healthy pregnant women. The disturbance in vasodilation state and testosterone can be attributed to malfunction placenta, and it varies according to gestational age and advancing disease state; being the best in G4 (normal pregnants in the third trimester), and being the worse in G2 (preeclamptics in the third trimester) as measured by NO. Alteration in electrolytes in preeclampsia includes increase in serum sodium and potassium which is accompanied by urinary retention of these cations expressed as urinary sodium and potassium per urinary creatinine. By contrary, serum corrected calcium and serum magnesium are significantly reduced in preeclamptics when compared with normal pregnants. All preeclamptics have certain factors that reduce vasodilation and enhance vasospasm supported by the finding of low ionized magnesium (which is essential for maintenance of vascular tone) and low ionized calcium (which is essential for the synthesis of endothelial-derived NO). This is further supported by the significant high elevation of the ratio between ionized calcium to ionized magnesium as well as the ratio between potassium to ionized magnesium. The inhibitory effect of testosterone on NO production is supported by negative correlation between these parameters; however, the positive correlation between ionized calcium and NO demonstrate the stimulatory effect of ionized calcium on NO production. The regulatory effect of NO on fluid balance is supported by the positive correlation between NO and urinary sodium excretion indicating that NO had different effects on renal tubular reabsorption of sodium. In conclusion, preeclamptics (in different gestational age groups) experience vasospasm, hyperandrogenemia, altered electrolytes and mineral status, with no difference in estrogen and progesterone when compared with healthy pregnants matched with their age and gestational age. The suggested mechanisms underlying these events are discussed.