Effect of a fibrin-derived vasoactive peptide on pulmonary angiotensin converting enzyme activity and on pressure responses to bradykinin.
Decreased angiotensin converting enzyme (ACE) activity is a common finding in patients with adult respiratory distress syndrome and in animal models of lung injury. The nature of this effect is unknown. Intravascular fibrin, also a common finding in lung injury, is degraded to small peptides by proteolytic enzymes. Peptide 6A, corresponding to amino acid residues 43 to 47 of the B beta chain of fibrin(ogen), is produced by plasmin degradation of fibrin and has been shown to inhibit ACE in vitro. We investigated the effect of this peptide on the pulmonary hydrolysis of a synthetic ACE substrate, benzoyl-phenylalanyl-alanyl-proline, in anesthetized rabbits and in isolated, perfused rabbit lungs. Peptide 6A caused a reversible, dose-dependent inhibition of benzoyl-phenylalanyl-alanyl-proline hydrolysis. It also potentiated the increase in pulmonary arterial pressure and the decrease in systemic arterial pressure due to bradykinin (BK), as well as the increase in pulmonary artery pressure due to BK in isolated lungs. The amount of BK needed to increase pulmonary arterial pressure was about 1000-fold larger in the isolated lung than in the intact animal. Peptides of this type might contribute to decreased ACE activity in patients with adult respiratory distress syndrome and may potentiate BK-mediated hemodynamic changes in these patients.
Department of Medicine, Rhode Island Hospital, Providence.
R
R
Moalli
K
K
Saldeen
T
T
Saldeen
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005337:Fibrin / Q000494:pharmacology*; D008168:Lung / Q000201:enzymology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D010446:Peptide Fragments; D005337:Fibrin; D001920:Bradykinin