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

Early Hum Dev. 2009 Sep;85(9):589-94. doi: 10.1016/j.earlhumdev.2009.06.005. Epub 2009 Jul 16.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin Receptor Antagonists
  • Animals
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Benzimidazoles / adverse effects
  • Benzimidazoles / therapeutic use
  • Biphenyl Compounds
  • Blood Pressure / drug effects
  • Female
  • Fetal Development / drug effects
  • Fetal Heart / drug effects
  • Fetal Heart / embryology
  • Fetal Heart / physiology
  • Fetus / drug effects
  • Fetus / physiology
  • Glutamyl Aminopeptidase / adverse effects
  • Glutamyl Aminopeptidase / therapeutic use*
  • Humans
  • Hydralazine / adverse effects
  • Hydralazine / therapeutic use
  • Hypertension, Pregnancy-Induced / drug therapy*
  • Kidney / drug effects
  • Kidney / embryology
  • Kidney / physiology
  • Magnesium Sulfate / adverse effects
  • Magnesium Sulfate / therapeutic use*
  • Pregnancy
  • Rats
  • Rats, Inbred SHR
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use*
  • Tetrazoles / adverse effects
  • Tetrazoles / therapeutic use

Substances

  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Benzimidazoles
  • Biphenyl Compounds
  • Recombinant Proteins
  • Tetrazoles
  • Hydralazine
  • Magnesium Sulfate
  • Glutamyl Aminopeptidase
  • candesartan