Tissue distribution of angiotensin converting enzyme and its inhibition by perindopril in pregnant rabbit and fetus.
The role of the renin angiotensin system (RAS) during pregnancy is not fully understood but numerous studies point to its importance in the homoeostasis of the fetal blood pressure and in the physiology of the fetal kidney near term. The aim of this study was to investigate the tissue distribution of angiotensin-converting enzyme (ACE) in the pregnant rabbit and its fetus and to assess the effect of Perindopril (PIL) a new ACE inhibitor on maternal and fetal tissue ACE activity. On day 28 of gestation, animals of the experimental groups were gavage-fed with 1 mg PIL or 10 mg PIL. ACE activity was assayed in tissue homogenates and serum with a radio-enzymatic method using (Gly-1-14C)-hippuryl-L-histidyl-leucine as specific substrate. In the kidney of control pregnant rabbit, decreasing values of ACE were found with a concentration gradient from the cortex to the inner papilla. ACE values in lung were comparable to those seen in kidney cortex. A significant effect of PIL was found with a percentage of inhibition of ACE activity in the renal cortex above 74% after 1 mg PIL and 88% after 10 mg PIL. In the control group, ACE activity was predominant in lung of fetuses. After maternal administration of 1 mg PIL, ACE activity fell significantly in fetal serum, placenta and fetal lung, but not in fetal kidney. Ten mg PIL produced a further significant decrease in ACE activity in fetal organs and serum. Plasma renin activity (PRA) was significantly stimulated after PIL administration in both mothers and fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)
Moulin
B
B
Institut National de la Santé et de la Recherche Médicale I.N.S.E.R.M. U-295, University of Rouen, France.
Morin
J P
JP
Seurin-Toutain
P
P
Borghi
H
H
Fillastre
J P
JP
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D005260:Female; D005333:Fetus / Q000201:enzymology*; D007211:Indoles / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D020913:Perindopril; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011817:Rabbits; D014018:Tissue Distribution
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D007703:Peptidyl-Dipeptidase A; D020913:Perindopril