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1 Hypertension and Vascular Disease Center, Wake Forest University, Winston Salem, North Carolina, United States;
2 Hypertension and Vascular Disease Center, Wake Forest University, Winston Salem, North Carolina, United States
3 Departments of Physiology and Biophysics, University of Mississippi, Medical Center, Jackson, Mississippi, United States
4 Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, United States
5 Hypertension Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
6 Department of Animal and Nutritional Sciences, University of New Hampshire, Durham, New Hampshire, United States
7 Dept of Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
* To whom correspondence should be addressed. E-mail: bbrosnih{at}wfubmc.edu.
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 angiotensin-(1-7) [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, 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 as compared to 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 as compared to 19 day NP. 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.
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