PULMONARY METABOLISM OF BRADYKININ ANALOGUES AND THE CONTRIBUTION OF ANGIOTENSIN CONVERTING ENZYME TO BRADYKININ INACTIVATION IN ISOLATED LUNGS

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Abstract
1 The activity and pulmonary metabolism of two peptides, 7-homo Pro-bradykinin and 8-homo Phe-bradykinin were studied in isolated systems. 2 Both analogues were about 50–70 times less active than bradykinin on the guinea-pig ileum and 70–160 times less active on isolated strips of cat terminal ileum. 3 The action of both analogues on guinea-pig ileum was potentiated (2.5-3.0 fold) by a bradykinin potentiating peptide (BPP9a) but less so than the action of bradykinin (4–5 fold). 4 Like bradykinin, the 8-homo Phe analogue was extensively inactivated (>90%) in a single passage through the pulmonary circulation of guinea-pig or rat isolated lungs and this inactivation was prevented by pre-treatment of the lungs with BPP9a. 5 The 7-homo Pro analogue was inactivated to a lesser degree in guinea-pig lungs (58%) and in rat lungs (89%) and its inactivation was not affected by BPP9a. 6 It is concluded that the 8-homo Phe analogue is a substrate for the dipeptidylcarboxypeptidase (angiotensin I converting enzyme) of lung, whereas the 7-homo Pro analogue is not a substrate. 7 There is about four times as much dipeptidylcarboxypeptidase activity in guinea-pig isolated lungs as there is in rat isolated lungs.