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 (NO₃^-) ingestion via beetroot juice (BRJ) on exercising muscle blood flow, and on plasma and muscle nitrate (NO₃^-), nitrite (NO₂^-) and cyclic GMP (cGMP) in male Sprague Dawley rats (~200 g, n=24) with monocrotaline-induced (60 mg/kg) PH. Muscle blood flow was assessed at rest and during treadmill running using fluorescent microspheres. Despite higher plasma NO₃^- (756 ± 118 vs 63 ± 22 μmol/L p=<0.001) and NO₂^- (0.63 ± 0.10 vs. 0.24 ± 0.04 μmol/L p=0.003), no difference between BRJ and PL was observed in either resting (p=0.88) or exercising (p=0.42) blood flow. Only NO₃^- was higher in BRJ vs. PL for both the soleus (sol: 261 ± 20 vs. 123 ± 18 vs μmol/kg, p=<0.0005) and vastus lateralis (VL: 176 ± 34 vs. 86 ± 14 μmol/kg, p=0.02), with no differences for NO₂^- (sol: 1.9 ± 0.2 vs.1.7 ± 0.3 μmol/kg, p=0.49; VL: 1.04 ± 0.2 vs. 1.03 ± 0.2 μmol/kg, p=0.97) or cGMP (sol: 4.8 ± 2.1 vs. 3.9 ± 1.5 vs. nmol/kg, p=0.22; VL 6.0 ± 3.8 vs. 5.8 ±3.2 nmol/kg, p=0.91). In a rat model of severe PH, acute BRJ dosing increases circulating and muscle NO₃^- but does not alter muscle blood flow. Absence of change in muscle NO₂^- and cGMP suggest insufficiently altered downstream NO signaling with BRJ supplementation.