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

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 O-2 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 (similar to 21%) and VC in 8 (similar to 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.