Masaaki Hasegawa

Brain natriuretic peptide levels in the umbilical venous plasma are elevated in fetal distress

We measured, by a specific radioimmunoassay, brain-natriuretic-peptide-like immunoreactive (BNP-LI) levels in the umbilical venous and arterial plasma of normal and distressed newborns. The indicated BNP-LI level in umbilical arterial plasma of normal newborns (3.5 +/- 0.9 fmol/ml, mean +/- SEM, n = 10) was significantly higher than that in umbilical venous plasma of the same newborns (2.2 +/- 0.5 fmol/ml). In the distressed newborns at term, the indicated BNP-LI level in umbilical venous plasma was 62.2 +/- 25.7 fmol/ml (n = 4), which was 19-fold higher than that of elective cesarean section cases (3.2 +/- 0.3 fmol/ml, n = 6; p < 0.05). The findings demonstrated that BNP was present in the human fetal circulation and that the plasma BNP level was elevated under fetal distress conditions.

The role of amniotic endothelin in human pregnancy

Endothelin (ET), a potent vasoconstrictor peptide, was originally isolated from culture medium of porcine aortic endothelial cells. Subsequently, ET was also reported to be produced by non-vascular tissues, and to be involved in various biological phenomena in these tissues. Recently, a high concentration of ET-1-like immunoreactivity (ET-1-LI) was detected in human amniotic fluid. Amnion tissue also contained a large amount of ET-1-LI, and cultured amnion cells secreted large amounts of ET-1-LI. The major component of ET-1-LI in these samples was ET-1. Moreover, the expression of prepro-ET-1 mRNA was detected in both amnion tissue and cultured amnion cells, indicating that ET-1 in the amniotic fluid originated from amnion cells. In addition, specific receptors for ET were detected in myometrium, decidua vera, chorion laeve and placenta, by both ligand binding analysis and Northern blot analysis. These findings suggest that ET-1 secreted from amnion cells plays a physiological role in human pregnancy. In this paper, the regulation of ET-1 production and expression of ET-receptors in avascular human amnion tissue are reviewed. The possible importance of amniotic ET in human pregnancy is also discussed.

Hyperapobetalipoproteinemia with compositional abnormality of LDL and IDL, a characteristic lipoprotein alteration in essential hypertension

The number and composition of apoprotein B (apoB)-containing lipoproteins that are very low density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) have been analyzed in subjects with essential hypertension who have no obesity and glucose intolerance. Twenty-three essential hypertensive subjects without diabetes mellitus and obesity were recruited. VLDL, IDL, LDL, and high-density lipoprotein (HDL) were separated by ultracentrifugation in the 23 hypertensive and 17 healthy subjects (control group). ApoB was determined by highly sensitive latex agglutination method in each lipoprotein fraction. There were no significant differences in age and body mass index between the hypertension and control groups. In hypertension, cholesterol levels significantly increased in plasma (13%, P < .05) and in LDL (20%, P < .05), but decreased in HDL (-14%, P < .05). Triglyceride significantly increased in plasma (66%, P < .05) and in VLDL (105%, P < .05). ApoB also significantly increased in plasma and all lipoprotein fractions except HDL. (plasma, 35%; VLDL, 94%; IDL, 82%; LDL, 42%; P < .05). With respect to lipoprotein composition, the ratio of cholesterol to apoB significantly decreased in IDL (P < .05) and LDL (P < .05). In essential hypertension, the number of apoB-containing lipoproteins (VLDL, IDL, LDL) all increased. A low ratio of cholesterol to apoB without changes in the ratio of triglyceride to apoB was noted in IDL and LDL, indicating the presence of small dense lipoprotein particles. Characteristic disorders of pure essential hypertension are characterized by hyperapobetalipoproteinemia and small dense LDL.

Endothelin-1-like immunoreactivity and endothelin receptors in the human placenta from normotensive and hypertensive pregnancies

The levels of endothelin-1-like immunoreactivity (ET-1-LI) and characteristics of endothelin receptors in the chorionic villous tissue of human placenta were determined. The ET-1-LI level in chorionic villous tissue obtained from normal term placenta was 2,450 +/- 940 pg/g wet weight (mean +/- SD, n = 4). Further analysis using gel permeation chromatography and reverse-phase high performance liquid chromatography showed that the main ET-1-LI constituent of ET-1-LI in this tissue was ET-1. Scatchard analysis of [125I]ET-1 binding to the membrane fraction of chorionic villous tissue obtained from term placenta showed high affinity receptor sites with an apparent dissociation constant (Kd) of 23.6 +/- 11.1 pM and a Bmax value of 388 +/- 238 fmol/mg protein (n = 5). The same binding study with [125I]ET 3 showed a Kd of 13.9 +/- 3.8 pM and a Bmax value of 176 +/- 78 fmol/mg protein (n = 5). These results suggest that both ET-A and ET-B receptors (ET-AR and ET-BR) are expressed in chorionic villous tissue. This finding was further confirmed by Northern blot analysis showing the expression of both ET-AR and ET-BR mRNAs in this tissue. ET-1-LI in the umbilical venous plasma of the newborns from women with pregnancy-induced hypertension (PIH) (38.3 +/- 10.4 pg/mL, n = 5) was significantly (P < 0.05) higher than that in the normal newborns from normotensive pregnant women (26.3 +/- 5.2 pg/mL, n = 12). However, in placental chorionic villous tissue obtained from PIH women, both ET-1-LI level and ET binding profile were not different from those in chorionic villous tissue from normotensive pregnant women. These results suggest that the abundant ET-ET receptor system is present in the placental chorionic villous tissue and that this system is not the major factor of the pathogenesis of placental dysfunction occurring in PIH because these systems are similar in normotensive and hypertensive pregnancies.

Clinical application of pulsatility index of flow volume to detect the hemodynamic changes in IUGR fetus

We attempted to assess feto-placental circulation in fetuses with intrauterine growth retardation (IUGR) by calculating the pulsatility index of flow volume (PIQ) based on the quantitative measurement of blood flow. Doppler sound was processed by an analog to digital converter and a frequency analyzer. Multiplication of frequency and signal strength of the Doppler sound at a certain time theoretically represents a value proportional to flow volume. Using this value, we calculated PIQ of the descending aorta, umbilical artery, and middle cerebral artery in normal fetuses, IUGR fetuses, and distressed fetuses during 24-41 weeks gestation. The PIQ of the fetal descending aorta in the IUGR fetus was significantly higher than that of the normal fetus. When cutoff value was set to mean +1 SD, abnormal PIQ was observed in 88% of IUGR fetuses. In contrast, the abnormal pulsatility index of maximal flow velocity (PIV) of the descending aorta was observed in only 62% of IUGR fetuses. In the distressed fetuses, both PIQ and PIV of the umbilical artery increased, and these indices of the middle cerebral artery markedly decreased. It is suggested that the increased PIQ of the descending aorta is an early indicator of changes in the fetal circulation in IUGR fetuses.