Year: 2004
Type: dissertation
Abstract: Introduction: Acute exercise, consisting of 1 to 3 bouts of 60 to 100 minutes, is \ncapable of preconditioning the myocardium against ischemia-reperfusion (I/R) injury. \nWe previously reported that elevated heat shock protein 70 (HSP70) is not required for \nthis cardioprotective effect. The agent or agents that trigger and mediate this \npreconditioning effect are still not understood, but may involve the production of \nreactive oxygen species (ROS) during exercise as a trigger, and the production of nitric \noxide (NO) by nitric oxide synthase (NOS) during I/R or uncoupling of mitochondrial \nrespiration as mediators. The purpose of the present studies was to determine the role of \nthese potential triggers and mediators in acute exercise-induced (AEI) cardioprotection. \nMethods: Rats were randomly assigned to seven treatment groups: sedentary (SED); \ntwo days of treadmill exercise at 20 m/min, 6-degree grade, for 60 minutes (RUN); \nsedentary and injected with 100 mg/kg N-(2-Mercaptopropionyl)glycine (MPG, a \npotent ROS scavenger) (SED/MPG); exercise and injected with MPG (RUN/MPG); \nsedentary then perfused with 100 µM Lω-Nitro-L-arginine methyl ester hydrochloride \n(L-NAME, a competitive inhibitor of NOS) (SED/L-N); exercise then perfused with LNAME \n(RUN/L-N); exercise in a 4°C environment (to prevent HSP70 increase) then \nperfused with L-NAME (CRUN/L-N). Twenty-four hours following the second \nexercise bout, or MPG injection, isolated-perfused working hearts were subjected to \n22.5 minutes of global ischemia followed by 30 minutes of normoxic reperfusion. \nPortions of left ventricle were analyzed for several putative mediators of exerciseinduced \ncardioprotection including: HSP70, inducible (iNOS) or endothelial (eNOS) \nNOS, manganese superoxide dismutase (MnSOD), and catalase. Results: All exercise \ngroups displayed improved recovery of cardiac function vs. sedentary groups, which \nwas not inhibited by MPG injection or L-NAME perfusion. Also, all exercise groups \nhad improved efficiency post-ischemia, suggesting that uncoupling does not mediate \nAEI cardioprotection. The only increases in protein expression were: HSP70 in RUN, \nRUN/MPG, and RUN/L-N; eNOS in CRUN/L-N; and catalase in SED/MPG and \nRUN/MPG. Conclusions: AEI cardioprotection appears to not be triggered by ROS \nproduction, is mediated by changes independent of eNOS or catalase expression and \nuncoupling, and can occur in the absence of increases in HSP70, MnSOD, and iNOS.
Author: Ryan P. Taylor
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2273758884