METHOD AND MATERIAL: Fresh, vaginally delivered placentae from ten normotensive pregnant women and nine women with pre-eclampsia were carefully dissected and 4 gm each of amnion, chorion laeve, placental plate chorion, fetal placenta (fetal surface of the placenta) and maternal placenta (surface of the placenta attached to the uterine wall) were obtained. These tissues were then thoroughly washed in a 0.5 M phosphate buffer, pH 7.5, at room temperature and then individually homogenized for one minute in 4 ml of the same buffer. After centrifugation the supernatant was removed. The pellet was re-suspended in buffer, re-homogenized and then centrifuged. The supernatant was removed and the procedure was repeated once again and the three supernatants of each tissue were pooled. Endothelin-1 was estimated by RIA. All results are presented as mean+/-SEM. Statistical analysis was performed using students 't' test for unpaired samples and a 'p' value of <0.05 was considered significant.
RESULTS: In tissues from normotensive pregnant women, no significant differences were evident in endothelin-1 concentrations in the chorion laeve, fetal placenta and maternal placenta but were significantly higher than those in the amnion and placental plate chorion (p<0.01). In tissues from pre-eclamptic women, no significant differences were evident between endothelin-1 concentrations in the chorion laeve, placental plate chorion and fetal placenta. Mean endothelin-1 concentration in the amnion and maternal placenta were significantly lower than those in chorion laeve, placental plate chorion and fetal placenta (p<0.01). Endothelin-1 concentrations were significantly higher in the amnion, chorion laeve, placental plate chorion and fetal placenta from women with pre-eclampsia when compared to tissues from normotensive pregnant women (p<0.01).
CONCLUSIONS: Endothelin-1 levels were significantly higher in the placental tissues from women with pre-eclampsia. Endothelin-1, being a powerful vasoconstrictor, could cause significant vasoconstriction in the placental vasculature, and alterations in endothelin-1 levels in placental vasculature may therefore have a role in the pathogenesis of pre-eclampsia.
RECENT FINDINGS: KCNJ5, ATP1A1, ATP2B3, CACNA1D, CTNNB1, and CACNA1H mutations are causal of primary aldosteronism. ARMC5 may cause bilateral lesions resulting in primary aldosteronism.LGR5, DACH1, and neuron-specific proteins are highly expressed in the zona glomerulosa and regulate aldosterone production.
SUMMARY: Most mutations causing primary aldosteronism are in genes encoding cation channels or pumps, leading to increased calcium influx. Genotype-phenotype analyses identified two broad subtypes of aldosterone-producing adenomas (APAs), zona fasciculata-like and zona glomerulosa-like, and the likelihood of under-diagnosed zona glomerulosa-like APAs because of small size. Zona fasciculata-like APAs are only associated with KCNJ5 mutations, whereas zona glomerulosa-like APAs are associated with mutations in ATPase pumps, CACNA1D, and CTNNB1. The frequency of APAs, and the multiplicity of causal mutations, suggests a pre-existing drive for these mutations. We speculate that these mutations are selected for protecting against tonic inhibition of aldosterone in human zona glomerulosa, which express genes inhibiting aldosterone production.