Kinin metabolism in the perfused ventilated rat lung. I: Bradykinin metabolism in a system modeling the normal, uninjured lung.
Bradykinin (BK) in an asanguinous salt solution was perfused through intact rat lung. BK concentration varied from 0.0015 to 89 microM. Below 17 microM, the amount degraded was greater than or equal to 90% of the dose. The BK fragment distributions expressed as a percentage of the BK dose degraded were constant. The BK fragments formed and percentage yields were Pro-Pro (2-3) 49%, Arg-Pro-Pro-Gly-Phe (1-5) 32%, Pro-Pro-Gly-Phe-Ser-Pro (2-7) 6%, Arg-Pro-Pro-Gly-Phe-Ser-Pro (1-7) 6%, Arg-Pro-Pro (1-3) 3% and residual BK 4%. Above 17 microM, the amount of BK degraded was not proportional to the dose. Captopril and enalaprilat inhibited BK degradation, and their maximum inhibitions were about 50% and 30%, respectively. The percentage yield of the 1-5 fragment was greatly reduced by both inhibitors, but the percentage yields of the 2-3 and 1-8 fragments were moderately increased. It was concluded that (1) the intact rat lung itself has a very large capacity to degrade BK in the range of 2 mumoles/min/kg body weight; (2) two major and several minor enzyme pathways exist to degrade BK; (3) the relative contributions of these pathways to overall BK degradation remain essentially constant over a bradykinin concentration range from 0.0015 to 17 microM; (4) ACE/kininase-II catalyzed hydrolysis is one of the major pathways but is not the single major route for BK degradation; and (5) the other major BK degradation pathway involves enzymes cleaving the Arg1-Pro2 and Pro3-Gly4 bonds of BK.
Baker
C R
CR
Department of Surgery, Texas Tech University School of Medicine, Lubbock 79430.
Little
A D
AD
Little
G H
GH
Canizaro
P C
PC
Behal
F J
FJ
D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000737:chemistry / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D000806:Angiotensin-Converting Enzyme Inhibitors; D010446:Peptide Fragments; D001920:Bradykinin