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Brief Exposure to Intracoronary Bradykinin at Reperfusion Limits Infarct Size in Isolated Rabbit Hearts by a Mechanism That Involves Both Free Radical Production and PKC
Author(s) -
Davis Amanda Marie,
Downey James M.,
Cohen Michael V.
Publication year - 2008
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/fasebj.22.1_supplement.750.11
Subject(s) - bradykinin , bradykinin receptor , protein kinase c , medicine , ischemia , reperfusion injury , chelerythrine , pharmacology , cardiology , chemistry , signal transduction , biochemistry , receptor
Bradykinin given at reperfusion following ischemia reduces infarct size. We determined if PKC and free radicals, signaling components involved in ischemic postconditioning, are also used by bradykinin. We also determined the minimum bradykinin infusion time required to be protective. Isolated rabbit hearts underwent 30 min coronary branch occlusion followed by 2h of reperfusion. 100 nM bradykinin was included in the perfusate for the first 60 min of reperfusion. Antagonists, when used, were present for the first 20 min of reperfusion. Bradykinin reduced infarct size from 32±4% of the risk zone in control to 11±3% (P<0.05). The scavenger 2‐mercaptopropionyl glycine (MPG), 300 uM, blocked bradykinin's protection (31±4%). The PKC antagonist chelerythrine (2.8 uM) also abrogated protection (29±3%). Infusing bradykinin for 15 min was still protective (17±3%). However, only 7 min of bradykinin did not protect (30±5%). We conclude that, like postconditioning, protection from bradykinin at reperfusion involves both redox signaling and PKC activation. While bradykinin may be too hypotensive to use intravenously, this drug could be given directly into a patient's coronary artery following percutaneous coronary intervention since the heart only needs to be exposed to bradykinin for 15 min. Work funded by NIH grant: HL 020648.