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1 Department of Biomedical Sciences and Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA
2 Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada
* To whom correspondence should be addressed. E-mail: woodmanc{at}missouri.edu.
We tested the hypothesis that exercise training (Ex) attenuates the effects of hypercholesterolemia on endothelium-dependent relaxation in left anterior descending coronary arteries (LAD). Adult female pigs were fed a normal fat (NF) or high fat (HF) diet for 20 weeks. Four weeks after initiating the diet, pigs were trained or remained sedentary for 16 weeks yielding four groups of pigs: 1) NF sedentary (NF-Sed), 2) NF exercise-trained (NF-Ex), 3) HF sedentary (HF-Sed), and 4) HF exercise-trained (HF-Ex). Sensitivity (EC50) to bradykinin (BK) was impaired in HF-Sed arteries. Ex improved BK-induced relaxation such that the EC50 and maximal response to BK in HF-Ex arteries was not different from NF-Sed and NF-Ex. Acetylcholine (ACh)-induced constriction was less in HF-Ex arteries than in HF-Sed, NF-Sed, and NF-Ex. To determine the mechanism(s) by which HF and Ex affected responses to BK and ACh, vasoactive responses were assessed in the presence of L-NAME (to inhibit nitric oxide synthase), indomethacin (Indo; to inhibit cyclooxygenase), and L-NAME + Indo. L-NAME inhibited BK-induced relaxation in NF (not HF) arteries. Indo did not significantly alter relaxation to BK in NF arteries however relaxation was enhanced in HF-Sed arteries. Double blockade with L-NAME + Indo attenuated BK-induced relaxation in NF arteries and eliminated relaxation in HF arteries. Neither L-NAME nor Indo altered constrictor responses to ACh in NF or HF arteries, however double blockade with L-NAME + Indo attenuated constriction to ACh in NF-Ex arteries. Endothelium-independent relaxation to sodium nitroprusside was enhanced in HF-Sed and HF-Ex arteries. Collectively, these results indicate that HF impaired endothelial function in coronary arteries by impairing production of NO and by enhancing production of a constrictor that was inhibited by Indo. Ex attenuated the effects of hypercholesterolemia by improving NO-mediated, endothelium-dependent, relaxation and by reducing the influence of the Indo-sensitive constrictor.
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