Endurance exercise training improves endothelium-dependent relaxation in brachial arteries from hypercholesterolemic male pigs.
We tested the hypothesis that exercise (Ex) training attenuates hypercholesterolemia-induced impairment of endothelium-dependent relaxation (EDR) in brachial (Br) arteries of adult male pigs by enhancing nitric oxide (NO)-mediated EDR. Adult male pigs were fed a normal-fat (NF) or high-fat/cholesterol (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: 1) NF-Sed, 2) NF-Ex, 3) HF-Sed, and 4) HF-Ex. EDR of Br artery rings was assessed in vitro with acetylcholine (ACh) and bradykinin (BK). ACh- and BK-induced relaxation was not impaired by HF; however, relaxation responses were enhanced by Ex in NF and HF arteries. To determine the mechanism(s) by which Ex improved EDR, ACh- and BK-induced relaxation was assessed in the presence of N(G)-nitro-l-arginine methyl ester (l-NAME; to inhibit NO synthase), indomethacin (Indo; to inhibit cyclooxygenase), or l-NAME + Indo. ACh- and BK-induced relaxation was inhibited by l-NAME, and l-NAME + Indo, in all groups of arteries. Indo did not inhibit ACh-induced relaxation in any group but did inhibit BK-induced relaxation in HF-Ex arteries. In the presence of l-NAME or l-NAME + Indo, ACh- and BK-induced relaxation in HF-Ex arteries remained greater than in HF-Sed arteries. However, in the presence of Indo, ACh-induced relaxation in HF-Ex arteries was no longer greater than in HF-Sed arteries. These results indicate that EDR is not impaired by hypercholesterolemia in Br arteries from adult male pigs; however, Ex improves EDR in HF Br arteries by enhancing production of endothelium-derived hyperpolarizing factor and/or prostacyclin.
Department of Biomedical Sciences, University of Missouri, Columbia, 65211, USA. woodmanc@missouri.edu
Christopher R
CR
Woodman
Mark A
MA
Thompson
James R
JR
Turk
M Harold
MH
Laughlin
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001916:Brachial Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D001920:Bradykinin / Q000494:pharmacology; D051242:Caveolin 1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006937:Hypercholesterolemia / Q000503:physiopathology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010805:Physical Conditioning, Animal; D010807:Physical Endurance; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013552:Swine; D013556:Swine, Miniature; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D051242:Caveolin 1; D014665:Vasodilator Agents; D009599:Nitroprusside; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000109:Acetylcholine; D001920:Bradykinin