The effect of recombinant aminopeptidase A (APA) on hypertension in pregnant spontaneously hypertensive rats (SHRs).
ABSTRACT 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.
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.
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.
Our present study showed that APA is one of the candidates for antihypertensive agents in hypertension during pregnancy.
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Article: Animal models of preeclampsia.[show abstract] [hide abstract]
ABSTRACT: There have been many attempts to produce animal models that mimic the hypertensive disorders of pregnancy, especially preeclampsia, but most are incomplete when compared to the full spectrum of the human disease. This review assesses a number of these models, organized according to the investigators attempt to focus on a specific pathogenic mechanism believed to play a role in the human disease. These mechanisms include uterine ischemia, impairments in the nitric oxide system, insulin resistance, overactivity of the autonomic nervous and/or renin-angiotensin systems, activation of a systemic inflammatory response, and most recently, activation of circulating proteins that interfere with angiogenesis. In addition a model of renal disease that mimics superimposed preeclampsia is discussed. Defining these animal models should help in our quest to understand the cause, as well as to test preventative and therapeutic strategies in the management of these hypertensive disorders of pregnancy.Seminars in Nephrology 12/2004; 24(6):596-606. · 2.83 Impact Factor
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ABSTRACT: A 31-year-old primigravida with twins had spontaneous rupture of the membranes at 32 weeks' gestation. On admission, because of contractions, the mother was started on tocolytic magnesium sulfate (MgSO4) along with betamethasone and prophylactic antibiotics. About a day later, she was found to have magnesium toxicity. Her serum total magnesium level was 9.0 mg/dl. Tocolysis was immediately discontinued. At cesarean delivery the following day, twin A, a female, died at 30 minutes of age despite a vigorous resuscitation. Although the preceding fetal heart rate patterns had been reassuring and the umbilical blood gases were normal, quite unexpectedly, the Apgar scores were 1/1/0. An autopsy revealed no anatomic abnormalities. Twin B, a female who survived, was also intubated at delivery. During her stay in the Neonatal Intensive Care Unit, she was found to have modestly elevated levels of serum cardiotroponin T. In our opinion, it is probable that the death of twin A can be directly attributed to magnesium sulfate toxicity. Neonatologists who attend deliveries should be aware that unexpected death may occur in babies who were exposed to high doses of tocolytic MgSO4.Journal of Perinatology 07/2001; 21(4):261-2. · 2.25 Impact Factor
Article: Aminopeptidase A in human placenta.[show abstract] [hide abstract]
ABSTRACT: Aminopeptidase A (l-α-aspartyl(l-α-glutamyl)-peptide hydrolase, EC 188.8.131.52) was found in human placenta, partially purified from it and briefly characterized in comparison with the placental leucine aminopeptidase. The aminopeptidase A could be separated from leucine aminopeptidase after trypsin digestion followed by Sephacryl S-300 chromatography. The angiotensinase (EC 184.108.40.206) activity of aminopeptidase A in human placenta was confirmed by a biological method.Biochimica et Biophysica Acta 12/1981; 662(1):168-78. · 4.66 Impact Factor