The effect of recombinant aminopeptidase A (APA) on hypertension in pregnant spontaneously hypertensive rats (SHRs)

Background: We have tested the effects of aminopeptidase A (APA), MgSO4 and various conventional anti hypertensive drugs on hypertension in pregnant spontaneously hypertensive rats (SHRs) and examined the effects on both fetal heart and kidney. Methods: We used recombinant human APA, which has been recently shown to work as an antihypertensive agent in SHRs (n = 5). Each drug was administered from gestational day 10 to day 20 and each dose was increased daily up to 10 fold until the end of treatment except for MgSO4 (n = 5 per each group). Blood pressure (BP) was monitored and fetal kidneys and heart were histologically examined. Results: The anti hypertensive effects of the drugs were in the following order: hydralazine > aminopeptidase A and angiotensin receptor blockers (ARBs), candesartan > MgSO4 and methyldopa. Microscopic examination showed that fetal exposure to candesartan is associated with poor proximal tubular differentiation in the kidney and that to MgSO4 is associated with poor blood vessel formation in the heart, respectively. Conclusions: Our present study showed that APA is one of the candidates for anti hypertensive agents in hypertension during pregnancy. (C) 2009 Elsevier Ireland Ltd. All rights reserved.