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Dietary Nitrate Supplementation via Beetroot Juice Improves Muscle O 2 Delivery and Utilization Matching in Heart Failure Rats
Author(s) -
Craig Jesse C,
Colburn Trenton D,
Hirai Daniel M,
Poole David C,
Musch Timothy I
Publication year - 2017
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/fasebj.31.1_supplement.1019.11
Subject(s) - heart failure , medicine , nitric oxide , preload , nitrite , bioavailability , placebo , cardiology , myocardial infarction , nitrate , endocrinology , hemodynamics , chemistry , pharmacology , alternative medicine , organic chemistry , pathology
Chronic heart failure (CHF) results in derangements to the central and peripheral cardiovascular systems after an initial insult to the heart that triggers a chain of maladaptations throughout the body. Paramount to these maladaptations is a reduction in O 2 delivery capacity and a diminished ability to utilize the O 2 once it reaches the muscle. These changes are attributed, in part, to a reduced bioavailability of nitric oxide (NO). Beetroot juice (BR) supplementation, which increases NO through the nitrate (NO 3 )‐nitrite‐NO pathway, has emerged as a potentially powerful therapeutic for CHF patients because of its independent effects on both O 2 delivery and utilization. We tested the hypothesis that BR supplementation would enhance the muscle O 2 delivery to utilization ratio in CHF rats, particularly at the onset of muscle contractions. To test this hypothesis, CHF was induced in young adult Sprague‐Dawley rats (n = 6; female = 3, male = 3) by surgically‐induced myocardial infarction (MI). Following 3 weeks of recovery, rats were given BR ([NO 3 ] 1 mmol/kg/day, CHF+BR; n = 3) or placebo (CHF; n = 3) for 5 days. MI size was not different between groups (CHF 24±5, CHF+BR 26±5 %) nor was any other cardiac functional index (i.e., LVEDP and LVdp/dt) (p > 0.05 for both). The Oxyphor G4 was injected into the surgically exposed spinotrapezius muscle and phosphorescence quenching employed to determine the temporal profile of muscle O 2 partial pressure in the interstitial space (P int O 2 , determined by O 2 delivery to utilization ratio) at rest and during electrically‐induced contractions (180 s, 1 Hz, 6 V). Mean arterial pressure was reduced preceding the start of contractions with BR (CHF 102±5, CHF+BR 89±5 mmHg; p < 0.05); however baseline (resting) P int O 2 was not different between groups (CHF 15±3, CHF+BR 16±1 mmHg; p > 0.05). Kinetics analysis revealed no differences for the P int O 2 amplitude (CHF 13±3, CHF+BR 11±1 mmHg) or the time constant (CHF 7±1, CHF+BR 8±2 s) (both p > 0.05), but the time delay was increased in CHF+BR (CHF 6±1, CHF+BR 8±1 s; p < 0.05). P int O 2 was elevated for CHF+BR (p < 0.05; see shaded area in figure) during the on‐transition (8–32 s) such that the P int O 2 undershoot during contractions was attenuated with BR (CHF 9±2, CHF+BR 5±1 mmHg; p < 0.05). In agreement with our hypothesis, BR supplementation improved muscle O 2 delivery and utilization matching in CHF rats during the vital period at the onset of contractions. These results further substantiate the utility of BR supplementation as a therapeutic for CHF. Support or Funding Information NIH HL‐2‐108328Mean P int O 2 during contractions in heart failure rats. Data are presented as means ± SEM. Closed and open circles represent placebo and beetroot juice supplementation, respectively. * denotes p < 0.05. Shaded area indicates significant difference between conditions.