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Am J Physiol Regul Integr Comp Physiol 293: R169-R177, 2007. First published April 11, 2007; doi:10.1152/ajpregu.00387.2006
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RENAL HEMODYNAMICS AND CARDIORENAL INTEGRATION

Temporal-spatial expression of ANG-(1-7) and angiotensin-converting enzyme 2 in the kidney of normal and hypertensive pregnant rats

J. Joyner,1 L. A. A. Neves,1 J. P. Granger,2 B. T. Alexander,2 D. C. Merrill,1 M. C. Chappell,1 C. M. Ferrario,1 W. P. Davis,3 and K. B. Brosnihan1

1Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina; 2Department of Physiology, University of Mississippi Medical Center, Jackson, Mississippi; and 3Department of Animal and Nutritional Sciences, University of New Hampshire, Durham, New Hampshire

Submitted 2 June 2006 ; accepted in final form 3 April 2007

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.

renin-angiotensin system; pregnancy; reduced uterine perfusion pressure


Address for reprint requests and other correspondence: K. B. Brosnihan, The Hypertension and Vascular Research Center, Wake Forest Univ. School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157-1032 (e-mail: bbrosnih{at}wfubmc.edu)




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