title: Oxygen supply and nitric oxide scavenging by myoglobin contribute to exercise endurance and cardiac function.
abstract: Recent studies of myoglobin (Mb) knockout (myo-/-) mice have extended our understanding of Mb's diverse functions and have demonstrated a complex array of compensatory mechanisms. The present study was aimed at detailed analysis of cardiac function and exercise endurance in myo-/- mice and at providing evidence for Mb's functional relevance. Myo-/- isolated working hearts display decreased contractility (dP/dtmax 3883+/-351 vs. 4618+/-268 mmHg/sec, myo-/- vs. WT, P<0.005). Due to a shift in sympathetic/parasympathetic tone, heart rate is reduced in conscious myo mice-/- (615+/-33 vs. 645+/-27 bpm, myo-/- vs. WT, P<0.001). Oxygen consumption (VO2) under resting conditions (3082+/-413 vs. 4452+/-552 ml x kg(-1) x h(-1), myo-/- vs. WT, P<0.001) and exercise endurance, as determined by spiroergometry, are decreased (466+/-113 vs. 585+/-153 m, myo-/- vs. WT, P<0.01). Conscious myo-/- mice evaluated by echocardiography display lowered cardiac output (0.64+/-0.06 vs. 0.75+/-0.09 ml x min(-1) x g(-1), myo-/- vs. WT, P<0.001), impaired systolic shortening (60+/-3.5 vs. 65+/-4%, myo-/- vs. WT, P<0.001) and fail to respond to beta1-stimulation. Strikingly, the latter cardiac effects of Mb deficiency can be partially attenuated by NOS inhibition. Loss of Mb results in a distinct phenotype, even under resting conditions, and the importance of oxygen supply and nitric oxide scavenging by Mb is clearly demonstrated at the conscious animal level.
authors.affiliation: Medizinische Klinik I, RWTH Aachen, Aachen, Germany. mmerx@ukaachen.de
authors.forename: Marc W
authors.initials: MW
authors.lastname: Merx
authors.forename: Axel
authors.initials: A
authors.lastname: Gödecke
authors.forename: Ulrich
authors.initials: U
authors.lastname: Flögel
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schrader
mesh_terms: D000818:Animals; D001285:Atropine / Q000008:administration & dosage; D001794:Blood Pressure; D002302:Cardiac Output; D003326:Coronary Circulation; D004452:Echocardiography; D016166:Free Radical Scavengers; D006321:Heart / Q000502:physiology*; D006339:Heart Rate; D051379:Mice; D018345:Mice, Knockout; D009211:Myoglobin / Q000172:deficiency / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010101:Oxygen Consumption; D010807:Physical Endurance / Q000502:physiology*; D005082:Physical Exertion / Q000502:physiology
chemical_list: D016166:Free Radical Scavengers; D009211:Myoglobin; D009569:Nitric Oxide; D001285:Atropine; D019001:Nitric Oxide Synthase