Bradykinin metabolism in the liver and lung of the rat.
Bradykinin (BK) in an asanguinous salt solution was perfused through intact rat liver. The perfusate was delivered through the portal vein and was collected from the inferior vena cava. BK concentrations varied from 0.0030 to 38.0 microm. The liver had a large capacity to degrade BK and the system did not approach saturation until perfusate BK concentrations reached 60 microm. The quantitatively predominant BK fragments formed and the amount of each formed, expressed as a percentage of the BK degraded during a single transhepatic passage, were Pro-Pro, 74%; Arg-Pro-Pro-Gly-Phe, 15%; and Arg-Pro-Pro-Gly-Phe-Ser-Pro, 7%; the first is indicative of initial aminopeptidase-P cleavage of BK to yield Arg and des-Arg1-BK and the latter two are indicative of initial angiotension converting enzyme (ACE) cleavage of BK. On the other hand, while the perfused rat lung also had a large capacity to degrade BK, the quantitatively predominant BK fragments formed and the amount of each formed, again expressed as a percentage of BK metabolized during a single transpulmonary passage, were Pro-Pro, 47%; Arg-Pro-Pro-Gly-Phe, 35%; and Arg-Pro-Pro-Gly-Phe-Ser-Pro, 7%. Thus in rat liver the aminopeptidase-P pathway is the major route for BK degradation, whereas in rat lung the aminopeptidase-P and the ACE pathways exhibit nearly equal capacities to degrade BK.
Griswold
J A
JA
Department of Surgery, Texas Tech University School of Medicine, Lubbock, Texas 79430, USA.
Beall
C V
CV
Baker
C R
CR
Little
D T
DT
Little
G H
GH
Behal
F J
FJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001165:Arteriovenous Malformations / Q000378:metabolism; D001920:Bradykinin / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D001920:Bradykinin