Effect of pre-exercise dietary nitrate on skeletal muscle blood flow in a rat model of pulmonary hypertension.

Skeletal muscle dysfunction contributes to exercise intolerance in patients with pulmonary arterial hypertension (PAH). Reduced blood flow to skeletal muscle has been demonstrated in a rat model of the disease. We investigated the effect of acute nitrate ([Formula: see text]) ingestion via beetroot juice (BRJ) on exercising muscle blood flow, and on plasma and muscle nitrate ([Formula: see text]), nitrite ([Formula: see text]), and cyclic GMP (cGMP) in male Sprague Dawley rats (∼200 g, = 24) with monocrotaline-induced (60 mg/kg) pulmonary hypertension (PH). Muscle blood flow was assessed at rest and during treadmill running using fluorescent microspheres. Despite higher plasma [Formula: see text] (756 ± 118 vs. 63 ± 22 µmol/L, ≤ 0.001) and [Formula: see text] (0.63 ± 0.10 vs. 0.24 ± 0.04 µmol/L, = 0.003), no difference between BRJ and PL was observed in either resting ( = 0.88) or exercising ( = 0.42) blood flow. Only [Formula: see text] was higher in BRJ vs. PL for both the soleus (sol: 261 ± 20 vs. 123 ± 18 vs. µmol/kg, ≤ 0.0005) and vastus lateralis (VL: 176 ± 34 vs. 86 ± 14 µmol/kg, = 0.02), with no differences for [Formula: see text] (sol: 1.9 ± 0.2 vs. 1.7 ± 0.3 µmol/kg, = 0.49; VL: 1.04 ± 0.2 vs. 1.03 ± 0.2 µmol/kg, = 0.97) or cGMP (sol: 4.8 ± 2.1 vs. 3.9 ± 1.5 vs. nmol/kg, = 0.22; VL 6.0 ± 3.8 vs. 5.8 ± 3.2 nmol/kg, = 0.91). In a rat model of severe PH, acute BRJ dosing increases circulating and muscle [Formula: see text] but does not alter muscle blood flow. Absence of change in muscle [Formula: see text] and cGMP suggest insufficiently altered downstream NO signaling with BRJ supplementation. Muscle dysfunction in pulmonary hypertension (PH) includes impairment in blood flow. The use of dietary nitrate to increase blood flow and potentially improve exercise tolerance has not been studied in this population. We show that acute dietary nitrate supplementation does not increase directly measured muscle blood flow in a PH rat, despite increases in plasma nitrate and nitrite. Muscle nitrate is elevated, but other markers of nitric oxide signaling (nitrite and cyclic GMP) are unaltered.