Attenuated vascular responsiveness to noradrenaline release during dynamic exercise in dogs

During dynamic exercise, there is reduced responsiveness to alpha(1)- and alpha(2)-adrenergic receptor agonists in skeletal muscle vasculature. However, it is desirable to examine the sympathetic responsiveness to endogenous release of neurotransmitter, since exogenous sympathomimetic agents are dependent upon their ability to reach the abluminal receptor. Therefore, to further our understanding of sympathetic control of vasomotor tone during exercise, we employed a technique that would elicit the release of endogenous noradrenaline (norepinephrine) during dynamic exercise. Mongrel dogs (n = 8, 19-24 kg) were instrumented chronically with transit time ultrasound flow probes on both external iliac arteries. A catheter was placed in a side branch of the femoral artery for intra-arterial administration of tyramine, an agent which displaces noradrenaline from the nerve terminal. Doses of 0.5, 1.0 and 3.0 microg ml(-1) min(-1) of iliac blood flow were infused for 1 min at rest and during graded intensities of exercise. Dose-related decreases in iliac vascular conductance were achieved with these concentrations of tyramine. The reductions in iliac vascular conductance (means +/- S.E.M.) were 45 +/- 6 %, 30 +/- 4 %, 26 +/- 3 % and 17 +/- 2 %, for the 1.0 microg ml(-1) min(-1) dose at rest, 3.0 miles h(-1), 6.0 miles h(-1) and 6.0 miles h(-1), 10 % gradient, respectively. At all doses, the magnitude of vasoconstriction caused by administration of tyramine was inversely related to workload. We conclude that there is a reduced vascular responsiveness to sympathoactivation in dynamically exercising skeletal muscle.