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Title: The role of the renin-angiotensin-aldosterone system in normal and hypertensive pregnancy
Author: Weir, Ronald J.
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1973
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In view of the potent vasopressor action of angiotensin II and the powerful sodium-retaining effect of aldosterone, an investigation has been made of the role of these substances in normal and hypertensive pregnancy. Initially, the renin-angiotensin-aldosterone system was examined in a large number of normal pregnant women. This study mainly involved the estimation of the plasma concentrations of renin, renin-substrate, angiotensin II and aldosterone. Measurements were also made of plasma and urinary electrolytes; plasma proteins, colloid osmotic pressure and osmolality; blood urea; serum creatinine; plasma volume and haematocrit - some of these factors having been shown to be associated with changes in the renin-angiotensin-aldosterone system in non-pregnant situations. Many of these substances were measured concurrently and a number were estimated serially during pregnancy and the puerperium. Plasma concentrations of cortisol, corticosterone, 11-deoxycorticosterone (DOC) and progesterone were also measured in a number of women. The circulating levels of renin, renin-substrate, angiotensin II and aldosterone were found to be increased above the normal non-pregnant range in many of the women studied. The mean plasma concentrations of renin-substrate, angiotensin II and aldosterone increased significantly from the first to the third trimester, whereas mean plasma renin concentration fell significantly over the same period although it remained above the normal non-pregnant range. Following delivery of the foetus and placenta, plasma renin, angiotensin II and aldosterone concentrations returned to normal non-pregnant levels within two weeks. The administration of the oestrogen stilboestrol to suppress lactation was thought to account for the continuing high level of renin-substrate up to six weeks post partum. The plasma concentrations of cortisol and 11-deoxycorticosterone were generally elevated in the last trimester but most of the values for plasma corticosterone concentration were within the normal non-pregnant range throughout gestation. A significant positive correlation was found between plasma renin and aldosterone and between plasma renin-substrate and angiotensin II in the first trimester but not thereafter, while plasma renin-substrate and aldosterone showed the only significant correlation when cases at all stages of pregnancy were analysed. Therefore, in spite of the marked changes which occur, the relationships between the four major components of the renin-angiotensin-aldosterone system appear to be more complex in pregnancy than in other physiological and clinical situations. A speculative explanation for this lack of relationship might be the presence in the circulation of "chorionic renin" which could be inactive in the generation of angiotensin II but which might possibly be involved in the secretion of aldosterone by another pathway as yet unidentified. The present study has shown that in normal pregnancy a positive correlation exists between plasma sodium and aldosterone concentrations, suggesting that the increased aldosterone secretion is a primary event influencing sodium balance rather than a secondary effect of established sodium depletion.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available