1 To identify the roles of endogenous
kinins in prevention of
myocardial infarction (MI), we performed the permanent
ligation of coronary artery in rats. 2 The size of MI 12, 24, and 48 h after coronary
ligation in
kininogen-deficient Brown Norway Katholiek (BN-Ka) rats was significantly larger (49.7+/-0.2%, 49.6+/-2%, and 51.1+/-1%, respectively) than that of
kinin-replete Brown Norway Kitasato (BN-Ki) rats (42+/-2%, 38.5+/-4%, and 41.5+/-1%). 3
Hoe140, a
bradykinin (BK)
B(2) receptor antagonist injected (1.0 mg kg(-1), i.v.) half an hour before, and every 8 h after, coronary
ligation, significantly increased the size of MI in Sprague-Dawley rats.
Aprotinin, a
kallikrein inhibitor, which was infused intravenously (10,000 Units kg(-1) h(-1)) with an osmotic mini-pump, significantly increased the size of an MI 24 h after
ligation. 4 When evaluated using
microspheres, the regional myocardial blood flow around the necrotic lesion in BN-Ka rats 6 h after
ligation was reduced more than that in BN-Ki rats with MI by 41-46%. The same was true in Hoe140-treated BN-Ki rats. 5
FR190997, a nonpeptide
B(2) agonist, which was infused (10 microg kg(-1) h(-1)) into the vena cava of BN-Ka rats for 24 h with an osmotic mini-pump, caused significant reduction in the size of MI (38+/-3%), in comparison with the size in vehicle
solution-treated rats (51+/-3%). The size of MI in FR190997-treated BN-Ka rats was the same as in BN-Ki rats. 6 These results suggested that endogenous
kinin has the capacity to reduce the size of MI via
B(2) receptor signalling because of the increase in regional myocardial blood flow around the ischaemic lesion.