Chymase-derived angiotensin II and arrhythmias after myocardial infarction.
Mast cell-derived chymase seems to be important in the regulation of local angiotensin (A) II formation in cardiovascular tissues. In human heart, chymase accounts for 80% of A II formation. Therefore, the chymase-dependent A II pathway may play an important role in the pathogenesis of A II-related cardiovascular diseases. For example, cardiac chymase was activated earlier than ACE and this activation lasted longer than that of ACE after myocardial infarction (MI) in hamsters. Treatment with a specific chymase inhibitor treatment, but not an ACE inhibitor, improved post-MI survival as well as cardiac function and the extent of the beneficial effects was similar to that observed for an AT1-receptor antagonist treatment in this model. The survival benefit after MI seems to be related to an antiarrhythmic effect of the chymase inhibitor because chymase inhibition reduces the incidence of ventricular arrhythmias during periods of heart ischemia in a dog MI model. Thus, an antiarrhythmic effect of the chymase inhibitor may contribute to a reduction in mortality rate during the acute phase after MI.
Jin
Denan
D
Department of Pharmacology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
Takai
Shinji
S
Okamoto
Yukiko
Y
Muramatsu
Michiko
M
Miyazaki
Mizuo
M
D000804:Angiotensin II / Q000378:metabolism*; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D053818:Chymases; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D009203:Myocardial Infarction / Q000150:complications* / Q000201:enzymology; D012697:Serine Endopeptidases / Q000378:metabolism*
D000804:Angiotensin II; D012697:Serine Endopeptidases; D053818:Chymases