Conversion of angiotensin I to angiotensin II by chymase activity in human pulmonary membranes.
An aprotinin-insensitive, angiotensin II (Ang II)-forming chymase has recently been identified in human heart tissue. We studied the hydrolysis of Ang I in human lung membranes. The hydrolysis products Ang II, Ang III, Ang-(1-9), Ang-(2-9), Ang-(1-7) and Ang-(8-10) appeared in membrane preparations from four patients. Two metabolic pathways for the formation of Ang II were identified; one depending on ACE activity (1.4 nmol Ang II/min/mg membrane protein) and the other on serine protease activity (2.1 nmol/min/mg). The serine protease activity was inhibitable to only 30 +/- 8% (mean +/- SEM) by aprotinin, suggesting chymase activity to play a role in the Ang I-conversion of human lung.
Lindberg
B F
BF
Department of Clinical Pharmacology, Lund University Hospital, Sweden. Fredrik.Lindberg@klinfarm.lu.se
Gyllstedt
E
E
Andersson
K E
KE
D000368:Aged; D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D007611:Aprotinin / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D053818:Chymases; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000201:enzymology; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000378:metabolism*
D011480:Protease Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I; D007611:Aprotinin; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; D053818:Chymases