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



Journal Title

Journal ISSN

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Kansas State University


Chronic heart failure (CHF) reduces nitric oxide (NO) bioavailability and impairs skeletal muscle vascular control during exercise. Reduction of nitrite (NO[subscript]2-) to NO may impact exercise-induced hyperemia particularly in muscles with pathologically-reduced O[subscript]2 delivery. We tested the hypothesis that NO[subscript]2- 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. Following a >21 day recovery, mean arterial pressure (MAP, carotid artery catheter) and skeletal muscle BF (radiolabelled microspheres) were measured during treadmill exercise (20 m•min[superscript]-1, 5% incline) with and without NO[subscript]2- infusion. The myocardial infarct size (35 ± 3%) indicated moderate CHF. NO[subscript]2- infusion increased total hindlimb skeletal muscle VC (CHF: 0.85 ± 0.09, CHF+NO[subscript]2-: 0.93 ± 0.09 ml•min[superscript]-1•100g[superscript]-1•mmHg[superscript]-1, p<0.05) without changing MAP (CHF: 123 ± 4 mmHg, CHF+NO[subscript]2-: 120 ± 4 mmHg, p=0.17). Total hindlimb skeletal muscle BF was not significantly different (CHF: 102 ± 7, CHF+NO[subscript]2-: 109 ± 7 ml•min[superscript]-1•100g[superscript]-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 following NO[subscript]2- infusion were comprised of ≥63% type IIb+IId/x muscle fibers. These data demonstrate that NO[subscript]2- infusion can augment skeletal muscle vascular control during exercise in CHF rats. Given the targeted effects shown herein, a NO[subscript]2[superscript]--based therapy may provide an attractive “needs-based” approach for treatment of the vascular dysfunction in CHF.



Heart failure, Nitrite, Exercise, Muscle, Blood flow, Nitric oxide

Graduation Month



Master of Science


Department of Kinesiology

Major Professor

Timothy I. Musch