Short‐term exercise training enhances functional sympatholysis through a nitric oxide‐dependent mechanism

Key points Sympathetic nervous system activity causes tonic vasoconstriction in resting and contracting skeletal muscle. Vasoactive molecules released from the active skeletal muscle and/or endothelium have been shown to inhibit sympathetic vasoconstriction, a phenomenon defined as functional sympatholysis. A definitive mechanism responsible for functional sympatholysis has yet to be identified; however, nitric oxide (NO) appears to be involved. It is unknown whether exercise training alters the inhibition of sympathetic vasoconstriction and NO‐mediated sympatholysis in resting and contracting skeletal muscle. The present findings demonstrate that short‐term exercise training augments functional sympatholysis in a training‐intensity‐dependent manner through a NO‐dependent mechanism. These novel findings advance our understanding of the effects of exercise training on the regulation of sympathetic vasoconstriction in resting and contracting skeletal muscle. Abstract We tested the hypothesis that short‐term mild‐ (M) and heavy‐intensity (H) exercise training would enhance sympatholysis through a nitric oxide (NO)‐dependent mechanism. Sprague–Dawley rats ( n = 36) were randomly assigned to sedentary (S) or to M (20 m min −1 5% gradient) or H exercise training groups (40 m min −1 5% gradient). Rats assigned to M and H groups trained on 5 days week −1 for 4 weeks, with the volume of training being matched between groups. Rats were anaesthetized and instrumented for stimulation of the lumbar sympathetic chain and the measurement of arterial blood pressure and femoral artery blood flow. The triceps surae muscle group was stimulated to contract rhythmically at 30 and 60% of maximal contractile force (MCF). The percentage change of femoral vascular conductance (%FVC) in response to sympathetic stimulation delivered at 2 and 5 Hz was determined at rest and during contraction at 30 and 60% MCF. The vascular response to sympathetic stimulation was reduced as a function of MCF in all rats ( P < 0.05). At 30% MCF, the magnitude of sympatholysis (%FVC rest – contraction; Δ%FVC) was greater in H compared with M and S groups (Δ%FVC at 2 Hz, S, 9 ± 5; M, 11 ± 8; and H, 18 ± 7; and Δ%FVC at 5 Hz, S, 6 ± 6; M, 12 ± 9; and H, 18 ± 7; P < 0.05) and was greater in H and M compared with S at 60% MCF (Δ%FVC at 2 Hz, S, 15 ± 5; M, 25 ± 3; and H, 36 ± 6; and Δ%FVC at 5 Hz, S, 22 ± 6; M, 33 ± 9; and H, 39 ± 9; P < 0.05). Blockade of NO synthase did not alter the magnitude of sympatholysis in S during contraction at 30 or 60% MCF. In contrast, NO synthase inhibition diminished sympatholysis in H at 30% MCF and in M and H at 60% MCF ( P < 0.05). The present findings indicate that short‐term exercise training augments sympatholysis in a training‐intensity‐dependent manner and through an NO‐dependent mechanism.