Role of tissue kallikrein in the cardioprotective effects of ischemic and pharmacological preconditioning in myocardial ischemia.

Abstract

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.

• Authors: V Griol-Charhbili, E Messadi-Laribi, J L Bascands, D Heudes, P Meneton, J F Giudicelli, F Alhenc-Gelas, C Richer
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 19 Issue 9 Pg. 1172-4 (Jul 2005) ISSN: 1530-6860 [Electronic] United States
• PMID: 15860541 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• RNA, Messenger
• Receptor, Bradykinin B1
• Receptor, Bradykinin B2
• ramiprilat
• Tissue Kallikreins
• Ramipril

Topics

• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Ischemic Preconditioning, Myocardial
• Mice
• Mice, Inbred C57BL
• Myocardial Infarction (drug therapy, pathology)
• Myocardial Reperfusion Injury (prevention & control)
• RNA, Messenger (analysis)
• Ramipril (analogs & derivatives, pharmacology)
• Receptor, Bradykinin B1 (genetics, physiology)
• Receptor, Bradykinin B2 (genetics, physiology)
• Tissue Kallikreins (physiology)