Bradykinin inhibits development of myocardial infarction through B2 receptor signalling by increment of regional blood flow around the ischaemic lesions in rats.
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.
Ito
Hiroshi
H
Department of Pharmacology, Kitasato University School of Medicine, Kitasato 1-15-1, Sagamihara, Kanagawa 228-8555, Japan.
Hayashi
Izumi
I
Izumi
Tohru
T
Majima
Masataka
M
D000818:Animals; D001920:Bradykinin / Q000378:metabolism*; D065168:Bradykinin Receptor Antagonists; D003326:Coronary Circulation / Q000502:physiology*; D007704:Kininogens / Q000172:deficiency / Q000235:genetics; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011914:Rats, Inbred BN; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D065168:Bradykinin Receptor Antagonists; D007704:Kininogens; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D001920:Bradykinin