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Am J Physiol Heart Circ Physiol. 2015 Oct;309(8):H1354-60. doi: 10.1152/ajpheart.00421.2015. Epub 2015 Sep 14.

Effects of nitrite infusion on skeletal muscle vascular control during exercise in rats with chronic heart failure.

Author information

1
Department of Kinesiology, Kansas State University, Manhattan, Kansas.
2
Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas; and.
3
Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas; and Department of Kinesiology, Kansas State University, Manhattan, Kansas.
4
Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas; and Department of Kinesiology, Kansas State University, Manhattan, Kansas Musch@Vet.K-State.edu.

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.

KEYWORDS:

blood flow; disease; nitrate; nitric oxide

PMID:
26371165
PMCID:
PMC4666960
DOI:
10.1152/ajpheart.00421.2015
[Indexed for MEDLINE]
Free PMC Article

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