title: Exercise training increases basal nitric oxide production from the forearm in hypercholesterolemic patients.
abstract: The objective of this study was to investigate the effects of cycle training on basal nitric oxide (NO) production and endothelium-dependent dilator capacity in hypercholesterolemic patients in whom acetylcholine responsiveness is impaired. Nine sedentary hypercholesterolemic volunteers (total plasma cholesterol >6.0 mmol/L; 2 female) aged 44+/-3 years (mean+/-SEM) participated in the study. Subjects remained sedentary for 4 weeks and performed 4 weeks of home-based cycle training (3 x 30 minutes/week at 65% maximum oxygen consumption [VO(2)max]) in a randomized order. Arteriovenous nitrate/nitrite (NO(x)) gradient was assessed and plethysmography was used to measure the forearm blood flow responses to arterial infusions of acetylcholine, sodium nitroprusside, and N(G)mono methyl L-arginine. Training increased VO(2)max from 30.4+/-1.9 to 34.3+/-1.4 mL x kg(-1) x min(-1) (P=0.01). Intrabrachial diastolic blood pressure was reduced from 70+/-3 to 68+/-3 mm Hg (P=0.02) with training, whereas systolic pressure did not change. Plasma triglycerides and total, LDL, and HDL cholesterol were not different between interventions. In the sedentary state, there was a positive forearm arteriovenous difference in plasma NO(x) indicating net extraction (6.8+/-4.0 nmol x 100 mL(-1) x min(-1)), whereas in the trained state this difference was negative, indicating net production (-5.8+/-5.8 nmol x 100 mL(-1) x min(-1); P=0.03). N(G)mono methyl L-arginine, at a dose of 4 micromol/min, caused a greater vasoconstriction after training (79.6+/-3.4% versus 69.9+/-6.8%; P=0.05). Acetylcholine and sodium nitroprusside induced dose-dependent elevations in forearm blood flow that were unaffected by training. These data suggest that basal release of endothelium-derived NO is increased with 4 weeks of home based training in hypercholesterolemic patients, independently of lipid profile modification. This may contribute to the cardiovascular protective effects of exercise training, including reduced blood pressure.
authors.affiliation: Alfred and Baker Medical Unit, Baker Medical Research Institute, Prahran, Australia.
authors.forename: T V
authors.initials: TV
authors.lastname: Lewis
authors.forename: A M
authors.initials: AM
authors.lastname: Dart
authors.forename: J P
authors.initials: JP
authors.lastname: Chin-Dusting
authors.forename: B A
authors.initials: BA
authors.lastname: Kingwell
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D000328:Adult; D001642:Bicycling; D001794:Blood Pressure; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D015444:Exercise; D005260:Female; D005542:Forearm; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism*; D007269:Injections, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000008:administration & dosage; D010991:Plethysmography; D012039:Regional Blood Flow; D014655:Vascular Resistance; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage; D019323:omega-N-Methylarginine / Q000008:administration & dosage
chemical_list: D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine