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Oxygen supply and nitric oxide scavenging by myoglobin contribute to exercise endurance and cardiac function
Author(s) -
Merx Marc W.,
Gödecke Axel,
Flögel Ulrich,
Schrader Jürgen
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2886fje
Subject(s) - nitric oxide , myoglobin , contractility , medicine , cardiac function curve , chemistry , heart rate , cardiac output , endocrinology , vo2 max , oxygen , cardiology , hemodynamics , blood pressure , biochemistry , heart failure , organic chemistry
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 (VO 2 ) under resting conditions (3082±413 vs. 4452±552 ml*kg −1 *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*min −1 *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 β 1 ‐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.