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Role of tissue kallikrein in the cardioprotective effects of ischemic and pharmacological preconditioning in myocardial ischemia
Author(s) -
GriolCharhbili Violaine,
MessadiLaribi Erij,
Bascands JeanLou,
Heudes Didier,
Meneton Pierre,
Giudicelli JeanFrançois,
AlhencGelas François,
Richer Christine
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-3508fje
Subject(s) - cardioprotection , antagonist , kinin , ischemia , pharmacology , receptor antagonist , ischemic preconditioning , receptor , in vivo , chemistry , medicine , ramipril , endocrinology , bradykinin , biology , microbiology and biotechnology , blood pressure
Tissue kallikrein (TK), a major kinin‐forming enzyme, is synthesized in the heart and arteries. We tested the hypothesis that TK plays a protective role in myocardial ischemia by performing ischemia‐reperfusion (IR) injury, with and without ischemic preconditioning (IPC) or ACE inhibitor (ramiprilat) pretreatment, in vivo in littermate wild‐type (WT) or TK‐deficient (TK −/− ) mice. IR induced similar infarcts in WT and TK −/− . IPC reduced infarct size by 65% in WT, and by 40% in TK −/− ( P< 0.05, TK −/− vs WT). Ramiprilat also reduced infarct size by 29% in WT, but in TK −/− its effect was completely suppressed. Pretreatment of WT with a B2, but not a B1, kinin receptor antagonist reproduced the effects of TK deficiency. However, B2 receptor‐deficient mice (B2 −/− ) unexpectedly responded to IPC or ramiprilat like WT mice. But pretreatment of the B2 −/− mice with a B1 antagonist suppressed the cardioprotective effects of IPC and ramiprilat. In B2 −/− , B1 receptor gene expression was constitutively high. In WT and TK −/− mice, both B2 and B1 mRNA levels increased several fold during IR, and even more during IPC+IR. Thus TK and the B2 receptor play a critical role in the cardioprotection afforded by two experimental maneuvers of potential clinical relevance, IPC and ACE inhibition, during ischemia.