Do angiotensin-converting enzyme inhibitors directly stimulate the kinin B1receptor?
Copyright policy )Do angiotensin-converting enzyme inhibitors directly stimulate the kinin B1receptor?
It has been recently claimed that the human B1receptors for kinins bind angiotensin-converting enzyme (ACE) inhibitors via a potential zinc-binding domain and are pharmacologically stimulated by these drugs. We verified whether ACE inhibitors stimulate B1receptors in vitro. The isolated rabbit aorta or mouse stomach responded by negligible contractions to the application of captopril, enalaprilat, or zofenoprilat. The human isolated umbilical vein also failed to respond to enalaprilat. All of these preparations were responsive to the B1receptor agonists des-Arg9-bradykinin (BK) or Lys-des-Arg9-BK. Furthermore, enalaprilat applied continuously had no significant interaction with the effects of Lys-des-Arg9-BK on the rabbit aorta. Enalaprilat failed to stimulate [3H]arachidonate release, translocate the receptors (confocal microscopy), or stimulate ERK1/2 phosphorylation (immunoblot) in HEK-293 cells stably expressing the rabbit B1receptor conjugated to yellow fluorescent protein. The phospho-ERK1/2 content of arterial smooth muscle cells of human or rabbit origin was increased by treatment with Lys-des-Arg9-BK but not with enalaprilat. ACE inhibitors do not act as bona fide agonists of the kinin B1receptors.
- Université Laval Canada
- CHU de Québec-Université Laval Canada
Arachidonic Acid, Microscopy, Confocal, Angiotensin-Converting Enzyme Inhibitors, Aorta, Thoracic, In Vitro Techniques, Kallidin, Receptor, Bradykinin B1, Muscle, Smooth, Vascular, Phospholipases A, Cell Line, Mice, Inbred C57BL, Luminescent Proteins, Mice, Bacterial Proteins, Enalaprilat, Animals, Humans, Mitogen-Activated Protein Kinases, Phosphorylation, Muscle Contraction
Arachidonic Acid, Microscopy, Confocal, Angiotensin-Converting Enzyme Inhibitors, Aorta, Thoracic, In Vitro Techniques, Kallidin, Receptor, Bradykinin B1, Muscle, Smooth, Vascular, Phospholipases A, Cell Line, Mice, Inbred C57BL, Luminescent Proteins, Mice, Bacterial Proteins, Enalaprilat, Animals, Humans, Mitogen-Activated Protein Kinases, Phosphorylation, Muscle Contraction
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