Enhanced expression of Ang-(1-7) during pregnancy

Abstract

Pregnancy is a physiological condition characterized by a progressive increase of the different components of the renin-angiotensin system (RAS). The physiological consequences of the stimulated RAS in normal pregnancy are incompletely understood, and even less understood is the question of how this system may be altered and contribute to the hypertensive disorders of pregnancy. Findings from our group have provided novel insights into how the RAS may contribute to the physiological condition of pregnancy by showing that pregnancy increases the expression of both the vasodilator heptapeptide of the RAS, angiotensin-(1-7) [Ang-(1-7)], and of a newly cloned angiotensin converting enzyme (ACE) homolog, ACE2, that shows high catalytic efficiency for Ang II metabolism to Ang-(1-7). The discovery of ACE2 adds a new dimension to the complexity of the RAS by providing a new arm that may counter-regulate the activity of the vasoconstrictor component, while amplifying the vasodilator component. The studies reviewed in this article demonstrate that Ang-(1-7) increases in plasma and urine of normal pregnant women. In preeclamptic subjects we showed that plasma Ang-(1-7) was suppressed as compared to the levels found in normal pregnancy. In addition, kidney and urinary levels of Ang-(1-7) were increased in pregnant rats coinciding with the enhanced detection and expression of ACE2. These findings support the concept that in normal pregnancy enhanced ACE2 may counteract the elevation in tissue and circulating Ang II by increasing the rate of conversion to Ang-(1-7). These findings provide a basis for the physiological role of Ang-(1-7) and ACE2 during pregnancy.

Preeclampsia and angiotensin converting enzyme (ACE) I/D and angiotensin II type-1 receptor (AT1R) A1166C polymorphisms: association with ACE I/D polymorphism

“…25 In preeclampsia, perturbation of the reninangiotensin system is associated with an increased vascular responsiveness to angiotensin II. 26 Our present study indicated an association between ACE I/D polymorphism and a 1.89-fold increased risk of preeclampsia in the presence of DD genotype.…”

Regulation of angiotensin-converting enzyme 2 and Mas receptor by Ang-(1–7) in heart and kidney of spontaneously hypertensive rats

“…According to some previous investigations, concentration and excretion rate of urinary Ang-(1-7) were lower in untreated hypertensive patients, 26 and women with preeclampsia and increased blood pressure showed decreased plasma Ang-(1-7). 27 These studies suggested that endogenous levels of Ang-(1-7) changed according to different blood pressure backgrounds; therefore, infusion of external Ang-(1-7) to rats with different blood pressure level induced varied responses.…”

The role of ACE2, angiotensin-(1–7) and Mas1 receptor axis in glucocorticoid-induced intrauterine growth restriction

“…Binding of Ang II to its receptor AT1 stimulates decidualization and rapid trophoblast proliferation in early pregnancy indicating a role of Ang II in implantation [26][27][28]. On the other hand, in mid to late pregnancy, an increase in urinary and plasma levels of Ang-(1-7) and ACE2 were found as well as an increase in local placental/ uterine production and activity of ACE2 suggesting a role for Ang-(1-7) in the enhancement of placental-fetal blood flow and rapid fetal growth in mid to late gestation [29][30][31][32][33].…”