Exercise attenuates the effects of hypercholesterolemia on endothelium-dependent relaxation in coronary arteries from adult female pigs.
We tested the hypothesis that exercise training (Ex) attenuates the effects of hypercholesterolemia on endothelium-dependent relaxation in left anterior descending coronary arteries. Adult female pigs were fed a normal-fat (NF) or high-fat (HF) diet for 20 wk. Four weeks after the diet was initiated, pigs were trained or remained sedentary (Sed) for 16 wk, yielding four groups of pigs: 1) NF-Sed, 2) NF-Ex, 3) HF-Sed, and 4) HF-Ex. Sensitivity (EC(50)) to bradykinin (BK) was impaired in HF-Sed arteries. Ex improved BK-induced relaxation such that the EC(50) and maximal response to BK in HF-Ex arteries was not different from that in NF-Sed and NF-Ex. 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 N(G)-nitro-L-arginine methyl ester [L-NAME; to inhibit nitric oxide (NO) 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.
Woodman
Christopher R
CR
Department of Biomedical Sciences, The Dalton Cardiovascular Research Center, University of Missouri, Columbia 65211, USA. woodmanc@missouri.edu
Turk
James R
JR
Rush
James W E
JW
Laughlin
M Harold
MH
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006937:Hypercholesterolemia / Q000503:physiopathology*; D066298:In Vitro Techniques; D010805:Physical Conditioning, Animal / Q000502:physiology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001920:Bradykinin