title: Effects of nitrite infusion on skeletal muscle vascular control during exercise in rats with chronic heart failure.
abstract: Chronic heart failure (CHF) reduces nitric oxide (NO) bioavailability and impairs skeletal muscle vascular control during exercise. Reduction of NO2 (-) to NO may impact exercise-induced hyperemia, particularly in muscles with pathologically reduced O2 delivery. We tested the hypothesis that NO2 (-) infusion would increase exercising skeletal muscle blood flow (BF) and vascular conductance (VC) in CHF rats with a preferential effect in muscles composed primarily of type IIb + IId/x fibers. CHF (coronary artery ligation) was induced in adult male Sprague-Dawley rats. After a >21-day recovery, mean arterial pressure (MAP; carotid artery catheter) and skeletal muscle BF (radiolabeled microspheres) were measured during treadmill exercise (20 m/min, 5% incline) with and without NO2 (-) infusion. The myocardial infarct size (35 ± 3%) indicated moderate CHF. NO2 (-) infusion increased total hindlimb skeletal muscle VC (CHF: 0.85 ± 0.09 ml·min(-1)·100 g(-1)·mmHg(-1) and CHF + NO2 (-): 0.93 ± 0.09 ml·min(-1)·100 g(-1)·mmHg(-1), P < 0.05) without changing MAP (CHF: 123 ± 4 mmHg and CHF + NO2 (-): 120 ± 4 mmHg, P = 0.17). Total hindlimb skeletal muscle BF was not significantly different (CHF: 102 ± 7 and CHF + NO2 (-): 109 ± 7 ml·min(-1)·100 g(-1) ml·min(-1)·100 g(-1), P > 0.05). BF increased in 6 (∼21%) and VC in 8 (∼29%) of the 28 individual muscles and muscle parts. Muscles and muscle portions exhibiting greater BF and VC after NO2 (-) infusion comprised ≥63% type IIb + IId/x muscle fibers. These data demonstrate that NO2 (-) infusion can augment skeletal muscle vascular control during exercise in CHF rats. Given the targeted effects shown herein, a NO2 (-)-based therapy may provide an attractive "needs-based" approach for treatment of the vascular dysfunction in CHF.
authors.affiliation: Department of Kinesiology, Kansas State University, Manhattan, Kansas.
authors.forename: Angela A
authors.initials: AA
authors.lastname: Glean
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas; and.
authors.forename: Scott K
authors.initials: SK
authors.lastname: Ferguson
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas; and.
authors.forename: Clark T
authors.initials: CT
authors.lastname: Holdsworth
authors.affiliation: Department of Kinesiology, Kansas State University, Manhattan, Kansas.
authors.forename: Trenton D
authors.initials: TD
authors.lastname: Colburn
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas; and.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Wright
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas; and.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Fees
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas; and.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Hageman
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas; and Department of Kinesiology, Kansas State University, Manhattan, Kansas.
authors.forename: David C
authors.initials: DC
authors.lastname: Poole
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas; and Department of Kinesiology, Kansas State University, Manhattan, Kansas Musch@Vet.K-State.edu.
authors.forename: Timothy I
authors.initials: TI
authors.lastname: Musch
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D017079:Exercise Tolerance; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D006439:Hemodynamics; D006614:Hindlimb; D007261:Infusions, Intra-Arterial; D008297:Male; D009119:Muscle Contraction; D018763:Muscle Fatigue; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects* / Q000503:physiopathology; D009203:Myocardial Infarction / Q000150:complications; D009569:Nitric Oxide / Q000378:metabolism*; D005082:Physical Exertion; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D012977:Sodium Nitrite / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D009569:Nitric Oxide; D012977:Sodium Nitrite
keywords: blood flow; disease; nitrate; nitric oxide