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.
Chronic heart failure and nitrate supplementation: Impact on skeletal muscle vascular control in exercising rats