HISTOCHEMICAL EVALUATION OF PLACENTAL ANGIOTENSINASE-A IN PREECLAMPSIA - 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 occ urred in hypertensive complications of pregnancy compared with uncompl icated pregnancies. Biochemical and semiquantitative histochemical met hods 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 at e-coupling in cryostat sections of placental tissue samples from 32 pa tients with pre-eclampsia, 11 patients with pregnancy-induced hyperten sion 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 stud y by light microscopy (semiquantitative score method). Score levels we re related to relative frequencies of hypertensive disorders (proporti onal odds model) and correlated to the severity of gestational hyperte nsion (Spearman's rank correlation). After detection of enzyme activit y the same tissue samples were homogenized and used for kinetic fluoro metric measurements under the same substrate and buffer conditions as in enzyme histochemistry. Enhanced villous trophoblastic angiotensinas e A activity was significantly associated with an increased frequency of pre-eclampsia in pregnant women (cumulative odds ratio x theta(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 concomita nt proteinuria (r=0.44; P<0.01). Histochemical evaluation of fetal blo od vessels and biochemical measurements revealed no statistically sign ificant results. In conclusion this study demonstrates for the first t ime that increased villous trophoblastic angiotensinase A activity ind icates an increased likelihood of the presence of pre-eclampsia and th e severity of hypertensive disorders in pregnancy. (C) 1996 W. B. Saun ders Company Ltd