Temporal-spatial expression of ANG-(1-7) and angiotensin-converting enzyme 2 in the kidney of normal and hypertensive pregnant rats.
We recently demonstrated that renin-angiotensin system (RAS) overactivity during late gestation in rats is associated with increased kidney and urine levels of ANG-(1-7) and enhanced kidney immunostaining of ANG-(1-7) and angiotensin-converting enzyme 2 (ACE2). To understand the temporal-spatial changes in normal and hypertensive pregnancies, the renal distribution of ANG-(1-7) and ACE2 in association with kidney angiotensin peptides and ACE2 activity was examined in virgin, normal pregnant (NP; gestational days 5, 15, and 19) and reduced uterine perfusion pressure (RUPP at day 19) pregnant Sprague-Dawley rats. ANG-(1-7) and ACE2 immunocytochemical staining increased 1.8- and 1.9-fold and 1.7- and 1.8-fold, respectively, at days 15 and 19 of NP, compared with virgin rats. ANG-(1-7) and ANG II concentrations were increased in the kidney at 19 days of gestation. ACE2 activity measured using a fluorescent substrate was increased 1.9- and 1.9-fold in the cortex and 1.9- and 1.8-fold in the medulla at days 15 and 19 of NP. In the RUPP animals, ANG-(1-7) immunostaining and concentration were significantly decreased compared with 19-day NP rats. ACE2 activity was unchanged in the cortex and medulla of RUPP rats. In conclusion, during NP, the concurrent changes of ACE2 and ANG-(1-7) suggest that ACE2 plays an important role in regulating the renal levels of ANG-(1-7) at mid to late gestation. However, the decrease in renal ANG-(1-7) content in the absence of a concomitant decrease in ACE2 implicates the participation of other ANG-(1-7) forming or degrading enzymes during hypertensive pregnancy.
Joyner
J
J
The Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157-1032, USA.
Neves
L A A
LA
Granger
J P
JP
Alexander
B T
BT
Merrill
D C
DC
Chappell
M C
MC
Ferrario
C M
CM
Davis
W P
WP
Brosnihan
K B
KB
D000803:Angiotensin I / Q000096:biosynthesis*; D000085962:Angiotensin-Converting Enzyme 2; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D004958:Estradiol / Q000652:urine; D005260:Female; D005455:Fluorescent Antibody Technique; D046110:Hypertension, Pregnancy-Induced / Q000201:enzymology / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D010446:Peptide Fragments / Q000096:biosynthesis*; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis*; D011225:Pre-Eclampsia / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D012083:Renin / Q000378:metabolism; D014563:Urodynamics / Q000502:physiology; D014599:Uterus / Q000098:blood supply
D010446:Peptide Fragments; D000808:Angiotensinogen; D004958:Estradiol; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D012083:Renin; C118790:angiotensin I (1-7)