The renin-angiotensinogen reaction during pregnancy and oral contraception: estimation of kinetic parameters by an autologous plasma renin assay

Abstract

A method has been developed which allows estimation of the kinetic parameters of the plasma renin-angiotensinogen reaction from data obtained by autologous renin assays at several plasma dilutions. The quantitative aspects of the renin-angiotensin system were examined in 28 plasma samples from 23 healthy, normotensive pregnant women. They were compared with 20 women who were not pregnant, of whom 12 were taking oral contraceptives and eight were not. In the first 3 months of pregnancy, there was a sharp increase in plasma renin activity and concentration. Plasma angiotensinogen rose steadily throughout pregnancy. The higher concentrations of renin and angiotensinogen would lead to an increase in angiotensin formation with potentially adverse consequences. However, this increase may be reduced by the fall in the affinity between renin and angiotensinogen which is suggested by the present observation that the Michaelis-Menten constant (Km) attained values five to six times higher than those seen in women not taking oral contraceptives. The smaller increases in plasma renin and angiotensinogen induced by oral contraceptives were less effectively compensated by lower affinity. Circumstantial evidence is provided which suggests that the observed high Km values may be due to oestrogen/pregnancy-induced synthesis of an angiotensinogen with a lower affinity for renin.

Matrix Metalloproteinases as Drug Targets in Preeclampsia

“…Another important mechanism contributing for the systemic vasodilatation is a decreased vascular responsiveness to angiotensin II [36]. These changes initiate further baroreceptor-mediated neurohormonal events, including activation of the RAAS [14, 37–39], with a subsequent increase in body sodium and water retention. Alterations in cortisol, vasopressin, kallikreins, vascular endothelial growth factor (VEGF), atrial natriuretic peptide, and in the sympathetic nervous system may also mediate cardiovascular adaptations during pregnancy [27, 35].…”

Hepatic Angiotensinogen Gene Regulation in the Fetal and Pregnant Rat1

“…Among possible hormonal influences, we renin are increased during pregnancy (25,26). The elevation of postulated that steroid and thyroid hormones known to increase estrogens during pregnancy has been proposed as an explanation around the time of birth may stimulate fetal Ao gene expression for the increase in circulating Ao levels (26,27), implying an (4).…”

“…The discrepancy between deselected genes (12). The Ao gene, as described by Ohkubo et al creased gene expression and circulating Ao levels could be ex- (8), possesses homology with glucorticoid receptor-binding se-plained by the identification of multiple circulating forms of Ao quences in the 5'-flanking region and thus provides a basis for during pregnancy (27); at least one of the these Ao isoforms may have altered kinetics for renin (27). Altered clearance of these multiple isoforms could possibly explain the descrepancy between high circulating Ao levels and low Ao mRNA expression.…”

Implications for the offspring of circulating factors involved in beta cell adaptation in pregnancy

“…The circulating level of PL increases in proportion to gestational age in rodent and human pregnancy, correlates with an increase in beta cell proliferation and insulin secretion in rodents, and may also be involved in the increased beta cell function and expansion in human pregnancy , although proliferation only may play a minor role in humans . Angiotensinogen increases steadily throughout pregnancy and the renin–angiotensin system can regulate beta cell mass by balancing islet cell proliferation and apoptosis; diminished oxidative stress and inflammation have been reported .…”