Enhanced expression of Ang-(1-7) during pregnancy.
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.
Brosnihan
K B
KB
The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Wiston-Salem, NC, USA. bbrosnih@wfubmc.edu
Neves
L A A
LA
Anton
L
L
Joyner
J
J
Valdes
G
G
Merrill
D C
DC
D000803:Angiotensin I / Q000097:blood / Q000378:metabolism* / Q000652:urine; D000818:Animals; D015415:Biomarkers; D005260:Female; D006801:Humans; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism* / Q000652:urine; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism* / Q000652:urine; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy / Q000097:blood / Q000378:metabolism* / Q000652:urine; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology*
D015415:Biomarkers; D010446:Peptide Fragments; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C118790:angiotensin I (1-7)