Effects of neuronal nitric oxide synthase inhibition on resting and exercising hindlimb muscle blood flow in the rat

Nitric oxide (NO) derived from endothelial NO synthase (eNOS) is an integral mediator of vascular control during muscle contractions. However, it is not known whether neuronal NOS (nNOS)‐derived NO regulates tissue hyperaemia in healthy subjects, particularly during exercise. We tested the hypothesis that selective nNOS inhibition would reduce blood flow and vascular conductance (VC) in rat hindlimb locomotor muscle(s), kidneys and splanchnic organs at rest and during dynamic treadmill exercise (20 m min−1, 10% grade). Nineteen male Sprague–Dawley rats (555 ± 23 g) were assigned to either rest (n= 9) or exercise (n= 10) groups. Blood flow and VC were determined via radiolabelled microspheres before and after the intra‐arterial administration of the selective nNOS inhibitor S‐methyl‐l‐thiocitrulline (SMTC, 2.1 ± 0.1 μmol kg−1). Total hindlimb muscle blood flow (control: 20 ± 2 ml min−1 100g−1, SMTC: 12 ± 2 ml min−1 100g−1, P < 0.05) and VC (control: 0.16 ± 0.02 ml min−1 100 g−1 mmHg−1, SMTC: 0.09 ± 0.01 ml min−1 100 g−1 mmHg−1, P < 0.05) were reduced substantially at rest. Moreover, the magnitude of the absolute reduction in blood flow and VC correlated (P < 0.05) with the proportion of oxidative muscle fibres found in the individual muscles or muscle parts of the hindlimb. During exercise, total hindlimb blood flow (control: 108 ± 7 ml min−1 100 g−1, SMTC: 105 ± 8 ml min−1 100 g−1) and VC (control: 0.77 ± 0.06 ml min−1 100g−1 mmHg−1; SMTC: 0.70 ± 0.05 ml min−1 100g−1 mmHg−1) were not different (P > 0.05) between control and SMTC conditions. SMTC reduced (P < 0.05) blood flow and VC at rest and during exercise in the kidneys, adrenals and liver. These results enhance our understanding of the role of NO‐mediated circulatory control by demonstrating that nNOS does not appear to subserve an obligatory role in the exercising muscle hyperaemic response in the rat. A fundamental feature of the response to exercise is the robust increase in active muscle blood flow (i.e. hyperaemia) during muscular work. Nitric oxide (NO) is a highly active biological molecule and is known to be an important controller of the increase in blood flow with exercise. However, the relative importance of the different forms of the enzyme that produce NO (NO synthase, NOS) is not yet fully understood. This investigation identifies one form (neuronal NOS) as an essential controller of hindlimb muscle blood flow at rest but not during exercise. These results further our understanding of th