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), MgSO(4) and various conventional antihypertensive 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 MgSO(4) (n=5 per each group). Blood pressure (BP) was monitored and fetal kidneys and heart were histologically examined.


RESULTS
The antihypertensive effects of the drugs were in the following order: hydralazine>aminopeptidase A and angiotensin receptor blockers (ARBs), candesartan>MgSO(4) and methyldopa. Microscopic examination showed that fetal exposure to candesartan is associated with poor proximal tubular differentiation in the kidney and that to MgSO(4) is associated with poor blood vessel formation in the heart, respectively.


CONCLUSIONS
Our present study showed that APA is one of the candidates for antihypertensive agents in hypertension during pregnancy.
Ishii
Masakazu
M
Department of Medical Science of Proteases, Nagoya University School of Medicine, Showa-ku, Nagoya, Japan. masai@med.nagoya-u.ac.jp
Hattori
Akira
A
Numaguchi
Yasushi
Y
Ma
Xiuyang
X
Nagasaka
Tetsuro
T
Tsujimoto
Masafumi
M
Murohara
Toyoaki
T
Kobayashi
Hiroshi
H
Mizutani
Sigehiko
S
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005318:Fetal Heart / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D005333:Fetus / Q000187:drug effects / Q000502:physiology; D043384:Glutamyl Aminopeptidase / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006830:Hydralazine / Q000009:adverse effects / Q000627:therapeutic use; D046110:Hypertension, Pregnancy-Induced / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D008278:Magnesium Sulfate / Q000009:adverse effects / Q000627:therapeutic use*; D011247:Pregnancy; D051381:Rats; D011918:Rats, Inbred SHR; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011994:Recombinant Proteins; D013777:Tetrazoles; D006830:Hydralazine; D008278:Magnesium Sulfate; D043384:Glutamyl Aminopeptidase; C081643:candesartan