The role of bradykinin in cardiac functional protection after
global ischemia-reperfusion in the rat heart.
Brew, Elizabeth C., Max B. Mitchell, Thomas F. Rehring, Fabia Gamboni
-Robertson, Robert C. McIntyre, Jr, Alden H. Harken, and Anirban
Banerjee.
Department of Surgery, University of Colorado Health Sciences
Center, Denver, Colorado 80262
APStracts 2:0128H, 1995.
Cardiac preconditioning against ischemia-reperfusion (IR) can be
induced by transient ischemia (TI) and [alpha]1-adrenoreceptor
stimulation. Our study objective was to explore the mechanism of
endogenous preconditioning and address the role of protein kinase C
(PKC) activation in bradykinin-mediated cardiac functional
protection. Isolated rat heart was used to assess the effects of
exogenous bradykinin, TI, selective B2 receptor blocker and PKC
antagonism on cardiac functional recovery after a global IR injury.
Final recovery of developed pressure was improved in hearts treated
with bradykinin and TI compared to controls. Bradykinin- and TI
-mediated preconditioning was eliminated with coinfusion of the B2
receptor antagonist. Further evaluation of bradykinin-mediated
preconditioning revealed that PKC blockade also eliminated functional
protection. Immunofluorescent stains of bradykinin-treated hearts
demonstrated translocation and activation of specific PKC isoforms in
preconditioned heart. We conclude that TI-mediated preconditioning
involves intrinsic cardiac bradykinin and [alpha]1-adrenergic
receptor stimulation. Bradykinin, through the B2 receptor, initiates
a series of intracellular events culminating in the activation of
PKC.
Received 6 July 1994; accepted in final form 23 March 1995.
APS Manuscript Number H586-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 April 1995.