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Randal A. Skidgel, Sinisa Stanisavljevic, Ervin G. Erdös

Kinin- and angiotensin-converting enzyme (ACE) inhibitor-mediated nitric oxide production in endothelial cells

Keywords: B1 receptor, bradykinin, carboxypeptidase M, kallidin, kininase I, nitric oxide synthase

Carboxypeptidase cleavage of the C-terminal Arg of kinins generates specific agonists of the B₁ receptor. Activation of B₁ receptors produces nitric oxide via eNOS in bovine endothelial cells and iNOS in cytokine-stimulated human endothelial cells. Angiotensin-converting enzyme (ACE) inhibitors are direct agonists of B₁ receptors in endothelial cells, although they release NO via a different signaling pathway than peptide ligands in bovine cells. This brief review discusses carboxypeptidase M as a required processing enzyme for generating B₁ agonists, how ACE inhibitors and peptide ligands stimulate NO production and the evidence for, as well as some consequences of, the direct activation of B₁ receptors by ACE inhibitors.

Biological Chemistry, Walter de Gruyter

Print ISSN: 1431-6730
Volume: 387, 02/2006
Pages: 159 - 165

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