Functional Sympatholysis: Integrated Vascular Regulation in Active Skeletal Muscle
In experimental animals, sympathetic neural vasoconstriction is blunted in the vascular beds of contracting compared with resting skeletal muscle, and nitric oxide (NO) is thought to be the primary factor involved. To date, the only data in humans are derived from vasoconstrictor responses obtained via indirect measurements of muscle oxygenation during reflex increases in sympathetic nerve activity, and have supported a role for NO in mediating this blunted vasoconstriction during exercise.
To determine the role of NO in the blunted vasoconstrictor responses to endogenous norepinephrine release in contracting human muscle.
Forearm blood flow (FBF; doppler Ultrasound) and mean arterial blood pressure (MAP; brachial artery catheter) were measured, and forearm vascular conductance (FVC) calculated (FBF/MAP*100) during steady-state rhythmic handgrip exercise (10–15% MVC) and steady-state control non-exercise vasodilator infusions (adenosine). The vasoconstrictor responses to 2 doses of tyramine were determined during exercise and adenosine administration, before and after NO synthase (NOS) inhibition with L-NMMA (n = 6) or L-NAME (n = 4).
The percentage reductions in FVC to tyramine were significantly less during exercise (−21 ± 4 and −22 ± 3%) compared with adenosine (−53 ± 5 and −69 ± 5%; P < 0.001), despite similar steady-state FVC. The vasoconstrictor responses to tyramine were still significantly less during exercise after L-NMMA (−20 ± 2 and −22 ± 2%) and L-NAME (−15 ± 5 and −28 ± 2%) compared with adenosine (−42 ± 5 and −62 ± 5%). Importantly, local NOS inhibition did not reverse the blunted vasoconstrictor responses to tyramine observed during exercise.
Our preliminary results challenge the hypothesis that NO plays an obligatory role in the blunted sympathetic vasoconstrictor responses during rhythmic handgrip exercise in humans.