A new myocardial conversion of angiotensin I.
The therapeutic benefits of angiotensin-converting enzyme inhibitors in the treatment of hypertension, congestive heart failure, and atherosclerotic heart disease are undeniable. Recent studies, however, suggest that the cardioprotective effect produced by these drugs is complex and may not be solely related to inhibition of the generation of angiotensin II. An alternative pathway for the generation of angiotensin II from angiotensin I has been proposed, following the recent identification of a chymotrypsin-like protease (chymase) that may contribute to the formation of angiotensin II in human heart tissue. The enzyme is present in cardiac mast cells and displays unusual substrate specificity for the conversion of angiotensin I to angiotensin II. While biochemical studies have provided convincing evidence for a chymase-dependent production of angiotensin II, the contribution of this enzyme to the physiologic or pathological regulation of arterial pressure and cardiac function remains undetermined.
Ferrario
C M
CM
Hypertension Center, Bowman Gray School of Medicine, Winston-Salem, North Carolina.
Chappell
M C
MC
D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D053818:Chymases; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000201:enzymology*; D006333:Heart Failure / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012697:Serine Endopeptidases / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I; D012697:Serine Endopeptidases; D053818:Chymases