Histochemical evaluation of placental dipeptidyl peptidase IV (CD26) in pre-eclampsia: enzyme activity in villous trophoblast indicates an enhanced likelihood of gestational hypertensive disorders.

PROBLEM: To determine whether differences in placental dipeptidyl peptidase IV (DPP IV, CD26) activities occurred in hypertensive complicated pregnancies as compared with uncomplicated pregnancies. METHOD: DPP IV activity was detected with H-Gly-Pro-4M2NA as the substrate in placental cryostat sections from 65 patients with gestational hypertension and 67 patients with uncomplicated pregnancies. The graduated intensities of the reaction product in the villous trophoblast were scored semiquantitatively by light microscopy and were related to the relative frequencies of hypertensive disorders (proportional odds model). After detection of enzyme activity, the same tissue samples were homogenized and used for kinetic fluorometric measurements. RESULTS: Enhanced villous trophoblastic DPP IV activity was significantly associated with an increased frequency of proteinuric hypertension in pregnant women (cumulative odds ratio theta1 = 1.6; P < 0.01). CONCLUSION: This study demonstrates for the first time that increased villous trophoblastic DPP IV activity indicates an increased likelihood of the presence and of the severity of hypertensive disorders in pregnancy.

Histochemical evaluation of placental angiotensinase A in pre-eclampsia: enzyme activity in villous trophoblast indicates an enhanced likelihood of gestational proteinuric hypertension.

The aim of this study was to examine whether differences in placental angiotensinase A (glutamyl aminopeptidase, EC 3.4.11.7) activities occurred in hypertensive complications of pregnancy compared with uncomplicated pregnancies. Biochemical and semiquantitative histochemical methods were used and compared for their applicability. Angiotensinase A activity was detected using L-alpha glutamyl-4-methoxy-2-naphthylamide (alpha-Glu-MNA) as substrate and Fast Blue B salt for simultaneous azo-coupling in cryostat sections of placental tissue samples from 32 patients with pre-eclampsia, 11 patients with pregnancy-induced hypertension and 44 participants with uncomplicated pregnancies. The graduated intensity of reaction product in the villous trophoblast and in fetal blood vessels was evaluated semiquantitatively in a double-blind study by light microscopy (semiquantitative score method). Score levels were related to relative frequencies of hypertensive disorders (proportional odds model) and correlated to the severity of gestational hypertension (Spearman's rank correlation). After detection of enzyme activity, the same tissue samples were homogenized and used for kinetic fluorometric measurements under the same substrate and buffer conditions as in enzyme histochemistry. Enhanced villous trophoblastic angiotensinase A activity was significantly associated with an increased frequency of pre-eclampsia in pregnant women (cumulative odds ratio x 0(1) 6.37; P < 0.001) and showed significant correlations with the severity of gestational hypertensive disorders, represented by systolic (r = 0.31; P < 0.05) and diastolic (r = 0.34; P < 0.05 blood pressure and by concomitant proteinuria (r = 044; P < 0.01). Histochemical evaluation of fetal blood vessels and biochemical measurements revealed no statistically significant results. In conclusion this study demonstrates for the first time that increased villous trophoblastic angiotensinase A activity indicates an increased likelihood of the presence of pre-eclampsia and the severity of hypertensive disorders in pregnancy.

The extravascular contractile system in the human placenta. Morphological and immunocytochemical investigations.

In the human placenta, besides the fetal blood vessel system a second extravascular contractile system exists. It is localized in the chorionic plate and runs in a longitudinal direction and adjacent to fetal blood vessels into the stem villi, where it forms perivascular contractile sheaths. Characteristically, cells of the extravascular contractile system are extremely long and spindle-shaped and give rise to fine cell processes, by which they obviously contact each other or insert into the basement membrane of the trophoblast. They show immunoreactivity with desmin, vimentin, alpha-actin, myosin, nitric oxide synthase type I (brain form) and dipeptidyl peptidase IV. The ultrastructure suggests that cells of the extravascular contractile system are related to smooth muscle cells, including subpopulations with myofibroblastic features. In stem villi a few cells are nitric oxide synthase type I immunoreactive. These cells are thought to be specialized smooth-muscle-like cells of the extravascular contractile system or cells of the extravascular contractile system related to paraneurons that generate nitric oxide, which, in turn, may modulate the tone of perivascular contractile sheaths. The high dipeptidyl peptidase IV activity suggests that modulation of the extravascular contractile system may also occur by substance P.

Effects of the synthetic glucocorticoid triamcinolone acetonide on vasoactive hydrolases of the human placenta in vitro.

Therapy with glucocorticoids during pregnancy is still debated. Previously reported effects of glucocorticoid application in rats resemble certain symptoms of preeclampsia. Therefore, we studied in vitro the effects of the synthetic glucocorticoid triamcinolone acetonide soluble (0.1-10 mM) on placental alpha-glutamyl amino-peptidase, microsomal alanyl aminopeptidase, dipeptidyl peptidase IV, acetylcholinesterase and butyrylcholinesterase in purified trophoblast monolayers and villous explants from first trimester (n = 5) and term placentae (n = 9) using bio- and histochemical methods. In term placentae quantitative histochemistry (microdensitometry) of trophoblast monolayers revealed an increase of alpha-glutamyl aminopeptidase and microsomal alanyl aminopeptidase activity up to 149% and 126% respectively, after treatment with supraphysiological doses. In trophoblast monolayers from first trimester alpha-glutamyl aminopeptidase activity was not affected, whereas microsomal alanyl aminopeptidase activity increased by 25%. Dipeptidyl peptidase IV staining was reduced to 26%. Biochemical measurements of alpha-glutamyl aminopeptidase and microsomal alanyl aminopeptidase activity in homogenates of cultured villi revealed effects similar to those found by microdensitometry in trophoblast monolayers. In contrast, dipeptidyl peptidase IV activity increased in explants of term placentae by 47%. Acetyl- and butyrylcholinesterase activities were reduced in term placental villi by 38% and 40%, respectively. The data indicate that glucocorticoids may affect the activity of hydrolases which are thought to be involved in local placental blood pressure modulation.

[The extravascular contractile system of the human placenta: a new aspect for function of the organ?]. / Das extravasale kontraktile System der Humanplazenta: Ein neuer Aspekt für die Funktion des Organs?

In the chorionic plate and stem villi of the human placenta besides the fetal blood vessel system a second extravascular contractile system (EVCS) exists. The cells of this system contain contractile and intermediate filaments and are dipeptidyl peptidase-IV- and NO-synthase-type-I-(NOS)-immunoreactive. Therefore it can be assumed that these cells cleave the vasodilator Substance P (by DPP IV) and produce NO (by NOS) and may contribute to a modulation of the EVCS.

Enzyme histochemical evidence for the presence of potential blood pressure regulating proteases in cultured villous explants from human first trimester placentae.

The proteases dipeptidyl peptidase IV, angiotensinase A and microsomal alanyl aminopeptidase are present in the human term placenta where they may be involved in the local modulation of placental blood pressure. In order to establish an in vitro model system to study the significance of these proteases in disorders related to pregnancy-induced hypertension, the activity of the proteases was localized histochemically in cultured explants of villi from human first trimester placentae. These studies revealed a similar distribution pattern of the activity of the proteases of cryostat sections of first trimester placental villi and in cultured tissue of the same placentae. Dipeptidyl peptidase IV and angiotensinase A activity were present in cytotrophoblast cells and dipeptidyl peptidase IV activity was found in the syncytiotrophoblast, respectively. Additionally, the activity of the proteases was visualized in various populations of stromal cells. Comparing our results with former studies, the protease activity pattern in first trimester placentae was found to be the same as in term placentae. Despite morphological changes of the tissue after 14 d in culture the localization of the proteases remained unchanged up to 52 d of culture. The results suggest that placental explants may serve as a suitable in vitro model for experimental studies on the role of proteases in pregnancy-induced hypertension.

[Treatment of severe hypertension in pregnancy]. / Behandlung der schweren Hypertonie in der Schwangerschaft.

Treatment of severe hypertension in pregnancy, particularly in preeclampsia and eclampsia, is a great challenge to the obstetrician and requires prompt and expert management. Application of antihypertensive agents is limited during pregnancy because of possible side effects, particularly impairment of the fetal state. The following survey present a detailed discussion on the substances suitable for treating hypertensive emergencies in pregnancy and their side effects. Despite restricted therapeutic possibilities, safe and successful treatment of severe hypertension during pregnancy can best be performed with dihydralazine and diazoxide, which achieve their effect by reducing the peripheral vascular resistance. If the blood pressure cannot be adequately reduced with these substances, treatment can be continued with sodium nitroprusside. A critical discussion is presented in this connection on drugs such as clonidine and reserpine, which reduce pressure largely by central mechanisms and should no longer be applied in pregnant patients because of serious disadvantages. Consideration is also given to the special clinical problems associated with pheochromocytomas, and a concluding discussion deals with the perspectives of antihypertensive therapy in pregnancy.

[Recklinghausen disease and pregnancy]. / Morbus Recklinghausen und Schwangerschaft.

Morbus Recklinghausen is an autosomal dominant disease with a high rate of new mutations. Progression of the skin lesions and the development of severe preeclampsia are the most important complications during gestation. In the following paper three cases with Recklinghausen's disease in pregnancy are reported and the consequence of the complications as well as the importance of genetic counseling are discussed.