M K Kalenga

Determination of renin, angiotensin converting enzyme and angiotensin II levels in human placenta, chorion and amnion from women with pregnancy induced hypertension

OBJECTIVE Pregnancy induced hypertension has been shown to be associated with a normal or low activity of the maternal circulating renin–angiotensin system (RAS) but little is known of the local RAS in placenta and fetal membranes. The present study attempts to determine, at full term of human preeclamptic pregnancies, the activity of the chorioplacental renin–angiotensin system.

Down regulation of the angiotensin II receptor subtype AT2 in human myometrium during pregnancy

Samples of human myometrium have been collected during pregnancy and from non-pregnant women. Binding studies revealed the presence of a 50-fold higher density of angiotensin II AT2 receptor in the non-pregnant state than during gestation. Low levels of the AT1 receptor subtype (approx. 20 fmol/mg protein) were detected in both pregnant and non-pregnant myometrium. Outside pregnancy, the AT2 receptor accounted for greater than 95% of all angiotensin receptors, whereas during pregnancy the value dropped to about 40%. The down regulation of the human myometrial AT2 receptor during pregnancy may be related to the high hormonal content of the environment induced by gestation. The mechanism by which the AT2 receptor is regulated appears to be different to that of the AT1 receptor.

Angiotensin II and its different receptor subtypes in placenta and fetal membranes.

The recent discovery of a local renin-angiotensin system in trophoblastic tissues has raised many questions regarding its role in the physiology of normal gestation and its implications in the pathophysiology of hypertension during pregnancy. In this article, the authors first review the most interesting aspects of the chorioplacental renin-angiotensin system, dwelling on the tissue distribution of angiotensin II and its receptor subtypes in the placenta and fetal membranes of different species. The relationship between angiotensin II and other locally synthesized chorioplacental substances is also analysed and the therapeutic implications of phenomena observed in pregnancy-associated hypertension are discussed.

Angiotensin II induces human placental lactogen and pregnancy-specific beta 1-glycoprotein secretion via an angiotensin AT1 receptor.

The purpose of this work was to determine which subtype of angiotensin II receptors was involved in angiotensin II-induced human placental lactogen (hPL) and pregnancy-specific beta 1-glycoprotein (SP1) secretion from human placenta. The experiments were performed using placental explants and isolated trophoblast cells. They were pretreated with Dup753 (antagonist of angiotensin AT1 receptor), PD123319 (antagonist of AT2 subtype) or with CGP42112A (agonist of angiotensin AT2 receptor) before the addition of angiotensin II. The octapeptide angiotensin II significantly increased the hPL and SP1 release from both placental explants and isolated trophoblast cells. The angiotensin AT1 receptor antagonist Dup753 inhibited the angiotensin II-stimulated hPL and SP1 secretion in a dose-dependent manner but the AT2 specific ligands PD123319 and CGP42112A had no effect. This study indicates that the angiotensin AT1 receptor is the main mediator of angiotensin II in the stimulation of hPL and SP1 secretion from human placenta.