Angiotensin-converting enzyme activity and contractile effects of angiotensin I and II in human uteroplacental arteries☆

Abstract OBJECTIVE: Our purpose was to study local angiotensin-converting enzyme activity and the mechanical effects of angiotensin I and II in human uteroplacental arteries. STUDY DESIGN: Angiotensin-converting enzyme activity was measured by a simple radioimmunoassay with tritiated benzoyl-glycyl-glycyl-glycine as substrate in isolated human intramyometrial arteries from nonpregnant ( n = 8) and term pregnant women ( n = 8) and placental ( n = 8) stem villous arteries. Moreover, in these vessels the mechanical effects of angiotensin I and II were investigated in organ bath experiments. Endothelium-infact and endothelium-denuded arteries were used, and the integrity of the endothelium was examined by histologic studies. RESULTS: The activity of angiotensin-converting enzyme ranked the intramyometrial arteries from pregnant women > > intramyometrial arteries from nonpregnant women >fetal stem villous arteries. Angiotensin-converting enzyme activity was unaffected by removal of the endothelium. Angiotensin II 10 −5 mol/L produced contractile responses in the intramyometrial arteries without significant differences between arteries from nonpregnant and pregnant women. In fetal stem villous arteries the effects of angiotensin II 10 −5 mol/L were less pronounced. As for angiotensin II, the contractile responses to angiotensin I 10 −5 mol/L showed marked development of tachyphylaxis. In the endothelium-denuded preparations the contractile responses to angiotensin I 10 −5 mol/L were significantly enhanced in intramyometrial arteries from nonpregnant women but remained unchanged in intramyometrial arteries from pregnant women and in fetal stem villous arteries. In all preparations pretreatment with captopril or perindopril (10 −5 mol/L) markedly reduced angiotensin-converting enzyme activity, whereas no effects were observed on the contractile responses to angiotensin I. Saralasi 10 −5 mol/L completely abolished the contractile responses to angiotensin I and II. CONCLUSION: Local angiotensin-converting enzyme activity in human intramyometrial arteries seems to be markedly increased during pregnancy and shows marked differences between maternal and fetal uteroplacental arteries. High concentrations of angiotensin I may imply direct effects on the angiotensin II receptor independent of the local angiotensin-converting enzyme activity.