Renin-Angiotensin System and Placental Leucine Aminopeptidase as Angiotensinase during Pregnancy
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Pregnancy is characterized by an activation of the renin-angiotensin system. In the present study we compared the level of renin activity, angiotensin and angiotensin-degrading activity in pregnancy sera with each other, and discussed the role of placental aminopeptidase as an angiotensinase in the regulation of blood pressure.<BR>Plasma renin activity (PRA) and angiotensin I (A-I) were determined using a radioimmunoassay technique in sera of normal pregnant women at different stages of gestation. Plasma A-I level in normal pregnant women was higher than that in non-pregnant women, but the difference was much less striking than PRA, which may be related to notably increased renin substrate level. A-I and PRA levels gradually rose with the extension of the period of pregnancy in the early stage of pregnancy, either leveled off or lowered in the middle stage and significantly reduced at the 7th month, and tended to rise again in the late stage.<BR>It is well known that serum leucine aminopeptidase (LAP) or oxytocinase (cystine aminopeptidase, CAP) increases progressively with advancing gestation. Our previous studies revealed that the estimation of LAP in the presence of 0.02M L-methionine has permitted exclusive determination of placental LAP (P-LAP) activity existing in pregnancy serum regardless of the presence of apparently normal levels of serum LAP. Thus, it was shown that the assays of P-LAP and CAP manifest an identical enzyme activity.<BR>The serum levels of LAP activity using colorimetry and angiotensinase activity estimated based on the blood pressure of rat using bioassay were compared in pregnancy sera. It was found that angiotensinase appearing in pregnancy sera had the same properties as P-LAP, with respect to heat inactivation at 60° for 30 minutes and 0.02M L-methionine inhibition. Subsequently, studies were made to see the relationship between P-LAP activity as angiotensinase and blood pressure level in 10 pregnant women. Blood pressure was lower in the middle or late stage of pregnancy than in the early stage, but rose again in the late stage of pregnancy or immediately before delivery. Both PRA and A-I levels were in accordance with the number of months of pregnancy. The activity of P-LAP levels determined simultaneously with PRA and A-I levels displayed sharp increases in the middle and late stages of pregnancy, but slightly decreased before delivery. These results suggest that P-LAP may be of protective value for elevation in blood pressure. Furthermore, these fmdings are highly suggestive of Yman's hypothesis that P-LAP (CAP) as an angiotensinase would be involved in the regulation of blood pressure.
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