title: Effects of ACE inhibition on spontaneous and insulin-stimulated endothelin-1 secretion: in vitro and in vivo studies.
abstract: To evaluate the effect of angiotensin-converting enzyme inhibition on spontaneous and insulin-stimulated endothelin-1 (ET-1) secretion in vitro and in vivo, human endothelial cells derived from umbilical cord veins were cultured onto acellular collagen-coated permeable membrane, thus mimicking in vivo conditions with a luminal and abluminal side. Insulin (10(-6,-8,-9) mol/l) significantly stimulated ET-1 secretion by cultured cells (P < 0.05 starting from 2-h incubation). Captopril (10(-7,-8,-9) mol/l) significantly reduced both spontaneous and insulin-stimulated ET-1 secretion, while increasing nitric oxide production. Considering each cell side, captopril significantly inhibited the apical secretion of ET-1, while its effect on the basolateral compartment was modest. In the presence of D-Arg,[Hyp3,Thi5,8,D-Phe7]-bradykinin (10(-6) mol/l), a bradykinin B2 receptor antagonist, captopril had no effects on ET-1 and nitric oxide production and also when insulin was added to the culture media. With regard to in vivo experiments, oral captopril therapy (25 mg twice daily for 1 week) was given to normotensive (n = 5) and hypertensive (n = 6) subjects and significantly decreased plasma ET-1 concentration (normotensive subjects, before: 0.98 +/- 0.09 pg/ml; after: 0.55 +/- 0.08 pg/ml, P < 0.0001; hypertensive subjects, before: 1.05 +/- 0.03 pg/ml; after: 0.56 +/- 0.05 pg/ml, P < 0.0001). Transient hyperinsulinemia was accompanied by a significant rise in plasma ET-1 concentrations in both groups (P < 0.0001 at 180 and 210 min) before but not after captopril treatment. In conclusion, captopril inhibits both spontaneous and insulin-stimulated ET-1 secretion by endothelial cells, acting on angiotensin-converting enzyme bound to the luminal cell side. In vivo, captopril significantly reduces plasma ET-1 levels in both basal and insulin-stimulated conditions.
authors.affiliation: The University La Sapienza, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Desideri
authors.forename: C
authors.initials: C
authors.lastname: Ferri
authors.forename: C
authors.initials: C
authors.lastname: Bellini
authors.forename: G
authors.initials: G
authors.lastname: De Mattia
authors.forename: A
authors.initials: A
authors.lastname: Santucci
mesh_terms: D000328:Adult; D000650:Amnion; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D012016:Reference Values; D014471:Umbilical Veins
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D019332:Endothelin-1; D007328:Insulin; C053748:B 4162; D009569:Nitric Oxide; D002784:Cholesterol; D002216:Captopril; D001920:Bradykinin