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Am J Obstet Gynecol. 1996 May;174(5):1450-5.
Placental passage of angiotensin-converting enzyme inhibitors.

Reisenberger K, Egarter C, Sternberger B, Eckenberger P, Eberle E, Weissenbacher ER.

Department of Obstetrics and Gynecology, University of Vienna, Austria.

OBJECTIVE: Placental passage of the angiotensin-converting enzyme inhibitors temocapril and enalapril was investigated in a placental perfusion model. STUDY DESIGN: In an open system a placental lobe was perfused on both the maternal and the fetal side with a blood-free medium containing the test substances plus a reference substance on the maternal side. Six placentas were perfused with temocapril and five with enalapril. The drugs were measured by gas chromatography-mass spectrometry. RESULTS: Both angiotensin-converting enzyme inhibitors crossed the human placenta in the maternal-fetal direction in similar quantities. Temocapril showed the same pharmacokinetic characteristics as enalapril. CONCLUSIONS: This was the first study to quantify the placental transfer of angiotensin-converting enzyme inhibitors. These antihypertensive agents should not be taken during pregnancy, to avoid any potential hazards to the fetus.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9065110&dopt=Abstract

pharma.novartis.com

The purpose of this study was to determine whether angiotensin-converting enzyme is present in cultured human bronchial epithelial cells and which types of epithelial cells possess this enzyme. It is well known that serum promotes squamous differentiation of airway epithelial cell culture in vitro. We found that whole-cell homogenates of both basal (serum-untreated) and squamous-differentiated bronchial epithelial cells degraded hippuryl-L-histidyl-L-leucine, a synthetic substrate for angiotensin-converting enzyme. Analysis of RNA expression by reverse transcription-polymerase chain reaction (RT-PCR) showed the presence of mRNA for angiotensin-converting enzyme in both types of cells. In addition, we found that squamous cells secreted the enzyme into the culture medium more than basal cells did. Angiotensin-converting enzyme inhibitors (imidaprilat, enalaprilat) inhibited the enzyme activity in bronchial epithelial cells with an IC50 of 0.9-3.6 nM. Exogenously added bradykinin was degraded to bradykinin-(1-5), an inactive fragment, in the squamous cell cultures. Our data indicate the presence of angiotensin-converting enzyme in cultured human bronchial epithelial cells and also that the enzyme is secreted by squamous differentiated cells.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10323266&dopt=Abstract




Acta Biomed Ateneo Parmense. 1992;63(1-2):163-73.
Glomerular hyperfiltration in essential hypertension: hormonal aspects.

Regolisti G, Buzio C, Cavatorta A, De Martin L, Cavalli R, Perazzoli F, Coghi P, Cabassi A, Pucci F, Borghetti A.

Istituto di Clinica Medica e Nefrologia, Universita degli Studi, Parma.

Glomerular hyperfiltration is thought to play a pivotal role in causing renal damage in essential hypertension. An increase in glomerular filtration rate can be experimentally induced by an acute oral protein load through still unclarified mechanisms, although hormonal factors have been postulated; in already hyperfiltering nephrons, the capacity to further increase glomerular filtration rate upon stimulation with an acute protein load (i.e. renal functional reserve) would conceivably be reduced, even in the presence of apparently normal renal function. The present study aimed at assessing whether renal functional reserve is preserved and/or is affected by different antihypertensive drugs in essential hypertensive patients without signs of renal function impairment; moreover, we tried to highlight changes in the plasma levels of natriuretic and antinatriuretic hormones potentially involved in the modulation of renal hemodynamics under the chosen experimental conditions. Renal hemodynamic parameters, plasma renin activity, aldosterone and atrial natriuretic factor were measured in fourteen essential hypertensives submitted to an acute oral protein load, alone or with a concomitant administration of either nifedipine or enalapril, as compared with a control carbohydrate meal. Glomerula filtration rate and renal plasma flow rose slightly but not significantly following an acute oral protein load as compared with a carbohydrate meal; no changes were noted in plasma atrial natriuretic factor levels, whereas plasma renin activity decreased. When nifedipine was administered together with the protein meal, both glomerular filtration rate and renal plasma flow increased significantly; there were also, parallel increases in plasma renin activity and atrial natriuretic factor. Administration of enalapril was associated with a decrease in both glomerular filtration rate and renal plasma flow; plasma renin activity showed an expected marked rise, whereas the plasma levels of atrial natriuretic factor were only slightly but not significantly reduced and plasma aldosterone fell. In conclusion, our data suggest that in our patients renal functional reserve was blunted. Clear-cut hyperfiltration was brought about by administration of nifedipine together with a protein meal, whereas enalapril completely abolished even the small increase in glomerular filtration rate seen after protein meal alone. The concomitant alterations in plasma renin activity, aldosterone and atrial natriuretic factor seemed to play no major role in the determinism of the observed renal hemodynamic changes.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1340661&dopt=Abstract













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