A study of the temporal relationship between plasma high molecular weight angiotensinogen and the development of pregnancy-induced hypertension.

In addition to the normally prevalent low molecular weight angiotensinogen (LMrA), significant quantities of a high molecular weight angiotensinogen (HMrA) are present in the human pregnant state. Previous studies have documented that 47% of women who develop pregnancy-induced hypertension (PIH) have a significantly elevated plasma HMrA/LMrA ratio. The purpose of this study is to establish whether or not the increase in the HMrA/LMrA ratio precedes the development of hypertension. Serial plasma samples were collected from a group of women throughout their pregnancy. High molecular weight angiotensinogen and LMrA levels in the samples from these women were determined. Fifteen of these women developed PIH. Seven women in the PIH group had a significantly elevated plasma HMrA/LMrA ratio. There was no consistent relationship between the elevation of the HMrA/LMrA ratio and the onset of hypertension. Three women had an elevated HMrA/LMrA ratio before the development of hypertension. In one woman the two events occurred simultaneously, and in three women the HMrA/LMrA ratio was elevated only after the development of hypertension. The current study shows that the development of hypertension during pregnancy is not the primary biologic signal for elevation of the plasma HMrA/LMrA ratio. Other parameters associated with fetal distress or abnormal development of placental circulatory systems must be involved in increasing the HMrA/LMrA ratio. It is proposed that the elevation of the HMrA/LMrA ratio is a mechanism by which the placental tissue specific renin-angiotensin system is attenuated.

Quantitation of the five forms of plasma high molecular weight angiotensinogen in women with pregnancy-induced hypertension.

In the human pregnant state a high molecular weight form of angiotensinogen (HMrA) is present in significant quantities in addition to the usual low molecular weight angiotensinogen (LMrA). In a previous study involving a small number of white women, it was found that women who had developed pregnancy-induced hypertension (PIH) had significantly higher levels of plasma HMrA. It has been determined that there are five isoforms of HMrA. The objectives of this study were to expand the previous study with the inclusion of black women and to determine which isoform(s) of plasma HMrA are elevated in PIH. Plasma LMrA and HMrA were quantitated in 24 normotensive pregnant women and 65 women with PIH. The PIH group had higher levels of HMrA and somewhat lower levels of LMrA than the normotensive group. The HMrA/LMrA ratio was elevated in 47% of the PIH group. The five isoforms of HMrA were quantitated in plasma from 10 white women with PIH, 10 black women with PIH, and 6 normotensive pregnant white women. Half of both the white and black women with PIH had an elevated HMrA/LMrA ratio. The relative proportion of the HMrA isomers was similar in all groups. These studies show that half the women with PIH have a distinct abnormality in their renin angiotensin system. Both white and black women show this abnormality. In those women who have an elevated total HMrA, all five isoforms of HMrA are equally elevated.

High molecular weight angiotensinogen: a pregnancy associated protein.

Although it was previously recognized that human amniotic fluid contained appreciable quantities of angiotensinogen, it remained unknown what fraction of the total is high molecular weight angiotensinogen. Fractionation of human amniotic fluid showed that high molecular weight angiotensinogen represents the major component of total angiotensinogen; 58% for 11 normotensive pregnant women and 67% for 12 hypertensive pregnant women. In contrast to plasma where high molecular weight angiotensinogen is elevated in hypertensive pregnant women as compared to normotensive pregnant women, no such difference exists for amniotic high molecular weight angiotensinogen. Serum and amniotic fluid high molecular weight angiotensinogen were compared in six subjects, and no significant correlation was found. In fetal cord blood, high molecular weight angiotensinogen represented only 5.8% of the total angiotensinogen. The site of synthesis of high molecular weight angiotensinogen remains unknown but these data suggest that it is produced in the placenta or in the maternal uterine tissue. Therefore, we propose that human high molecular weight angiotensinogen should be classified as a pregnancy-associated protein.