Exercise training, indomethacin, and isoproterenol-induced myocardial necrosis in the rat.
It was hypothesized that endurance exercise training would attenuate isoproterenol-induced myocardial necrosis in the rat by increasing the concentration of prostacyclin in the myocardial vasculature. Rats were randomly assigned to exercise and control groups. Exercisers ran on a motorized treadmill 1 h.d-1, 5 d.week-1 for 14 weeks. Immediately following the training program subgroups of rats were injected with 4 mg.kg-1 indomethacin or saline. One day later, all rats were given a subcutaneous injection of isoproterenol (20 mg.kg-1); after another 24 h they were sacrificed. A decrease of myocardial creatine kinase (CK) activity was used as a marker for myocardial necrosis. Endurance exercise training attenuated the isoproterenol-induced decrease in myocardial CK relative to control by approximately 37% (exercise: 16.4 +/- 0.6 U.mg-1 protein; control: 10.5 +/- 0.6 U.mg-1 protein; p less than 0.05). Pretreatment with indomethacin decreased myocardial CK in the exercise-trained rats (indomethacin: 15.4 +/- 0.8 U.mg-1 protein; saline: 17.7 +/- 0.7 U.mg-1 protein; p less than 0.05), but not in the controls (indomethacin: 10.3 +/- 1.0 U.mg-1 protein; saline: 10.8 +/- 0.6 U.mg-1 protein; p greater than 0.05). The concentration of myocardial 6-keto-PGF1 alpha, a marker for prostacyclin, was not altered by exercise but, as expected, was reduced by indomethacin pretreatment (p less than 0.05). Thus, exercise training reduces myocardial damage caused by isoproterenol, but the evidence does not support the hypothesis that prostacyclin mediated this effect of training. Further research is needed to determine the extent to which exercise training-induced alterations in sensitivity to PGI2 or TXA2 affect myocardial damage from isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)
Brodowicz
G R
GR
Exercise Physiology Laboratory, Ohio State University, Columbus.
Lamb
D R
DR
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003402:Creatine Kinase / Q000032:analysis; D011464:Epoprostenol / Q000032:analysis; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009336:Necrosis; D009929:Organ Size / Q000187:drug effects; D010805:Physical Conditioning, Animal; D051381:Rats; D011919:Rats, Inbred Strains
D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D003402:Creatine Kinase; D007545:Isoproterenol; D007213:Indomethacin