Exercise training augments neuronal nitric oxide synthase‐mediated inhibition of sympathetic vasoconstriction in contracting skeletal muscle of rats

Key points Sympathetic nervous system activity causes tonic vasoconstriction in resting and contracting skeletal muscle. Nitric oxide (NO) has been shown to inhibit sympathetic vasoconstriction. NO derived from both the neuronal and endothelial isoforms of NO synthase (NOS) has been shown to contribute to the inhibition of sympathetic vasoconstriction. Our laboratory recently demonstrated that exercise training augmented NO‐dependent inhibition of sympathetic vasoconstriction. However, the NOS isoform responsible for the increase in NO‐mediated inhibition of sympathetic vasoconstriction following exercise training has not been established. The present findings demonstrate that exercise training improves neuronal NOS‐mediated inhibition of sympathetic vasoconstriction in contracting skeletal muscle. We tested the hypothesis that exercise training would increase neuronal nitric oxide synthase (nNOS)‐mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle. Sprague–Dawley rats (n = 18) were randomized to sedentary or exercise‐trained (40 m min−1, 5° grade; 5 days week−1 for 4 weeks) groups. Following completion of sedentary behaviour or exercise training, rats were anaesthetized and instrumented with a brachial artery catheter, femoral artery flow probe and stimulating electrodes on the lumbar sympathetic chain. The percentage change of femoral vascular conductance (%FVC) in response to sympathetic chain stimulations delivered at 2 and 5 Hz was determined at rest and during triceps surae muscle contraction before (control) and after selective nNOS blockade with S‐methyl‐l‐thiocitrulline (SMTC, 0.6 mg kg−1, i.v.) and subsequent non‐selective NOS blockade with l‐NAME (5 mg kg−1, i.v.; SMTC + l‐NAME). At rest, sympathetic vasoconstrictor responsiveness was greater (P 0.05) between exercise trained (2 Hz: −11 ± 4%FVC; 5 Hz: −21 ± 5%FVC) and sedentary rats (2 Hz: −7 ± 6%FVC; 5 Hz: −18 ± 10%FVC) in control conditions. SMTC augmented (P