Inhibition of angiotensin converting enzyme activity in cultured endothelial cells by hypoxia.
Endothelial cells in tissue culture degrade bradykinin and convert angiotensin I to angiotensin II. These are both functions of a single dipeptidyl hydrolase, angiotensin converting enzyme. Monolayer cultures were prepared from human, rabbit, pig, and calf vessels. Angiotensin converting enzyme activity was assessed by adding either bradykinin or angiotensin I to the cells in culture flasks, and measuring residual peptide over time by radioimmunoassay. Peptide degradation was inhibited by the specific converting enzyme inhibitor, SQ 20881. The flasks were equilibrated with varying hypoxic gas mixtures: hypoxia rapidly (less than 2 min) decreased enzyme activity and room air restored it as rapidly. The extent to which activity was reduced was a direct function of PO2 (r = 0.93, P less than 0.001), and there was no enzyme activity below a PO2 of 30 mm Hg. Four preparations were studied with respect to decrease in enzyme activity by hypoxia: (a) intact cells in monolayer, (b) sonicated cells, (c) sonicated cells from which converting enzyme was partially dissolved by a detergent, and (d) purified converting enzyme. Hypoxia had progressively less of an inhibiting effect on the enzyme activity of the preparations as the degree of cell integrity decreased. Hypoxia inhibits angiotensin converting enzyme activity in cultured endothelial cells, but the effect of hypoxia is not on the enzyme per se, but appears to be a unique characteristic of the endothelial cell.
D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002478:Cells, Cultured; D004727:Endothelium / Q000201:enzymology* / Q000648:ultrastructure; D006651:Histocytochemistry; D006801:Humans; D000860:Hypoxia / Q000201:enzymology* / Q000473:pathology; D008168:Lung / Q000166:cytology; D008855:Microscopy, Electron, Scanning; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D014470:Umbilical Cord / Q000166:cytology
D007703:Peptidyl-Dipeptidase A