Is sympathetic neural vasoconstriction blunted in the vascular bed of exercising human muscle?

Abstract

Sympathetic vasoconstriction of muscle vascular beds is important in the regulation of systemic blood pressure. However, vasoconstriction during exercise can also compromise blood flow support of muscle metabolism. This study tested the hypothesis that local factors in exercising muscle blunt vessel responsiveness to sympathetic vasoconstriction. We performed selective infusions of three doses of tyramine into the brachial artery (n= 8) to evoke endogenous release of noradrenaline (norepinephrine) at rest and during moderate and heavy rhythmic handgrip exercise. In separate experiments, tyramine was administered during two doses of adenosine infusion (n= 7) and two doses of sodium nitroprusside (SNP) infusion (n= 8). Vasoconstrictor effectiveness across conditions was assessed as the percentage reduction in forearm vascular conductance (FVC), calculated from invasive blood pressure and non‐invasive Doppler ultrasound blood flow measurements at the brachial artery. Tyramine evoked a similar dose‐dependent vasoconstriction at rest in all three groups, with the highest dose resulting in a 42‐46 % reduction in FVC. This vasoconstriction was blunted with increasing exercise intensity (e.g. tyramine high dose percentage reduction in FVC; rest −43.4 ± 3.7 %, moderate exercise −27.5 ± 2.3 %, heavy exercise −16.7 ± 3.6 %; P < 0.05). In contrast, tyramine infusion resulted in a greater percentage reduction in FVC during both doses of adenosine vs. rest (P < 0.05). Finally, percentage change in FVC was greater during low dose SNP infusion vs. rest (P < 0.05), but not different from rest at the high dose of SNP infusion (P= 0.507). A blunted percentage reduction in FVC during endogenous noradrenaline release in exercise but not vasodilator infusion indicates that sympathetic vasoconstriction is blunted in exercising muscle. This blunting appears to be exercise intensity‐dependent.

Neural control of muscle blood flow during exercise

“…However, perusal of the literature indicates that functional sympatholysis has not been a consistent finding. Overall, a continuum of changes in vascular responsiveness to SNA in exercising muscle has been reported, ranging from well-preserved vasoconstriction to complete inhibition of vasoconstriction (20,35,41,42,59,66,68,71,72,80,83,86,87,90,91,93,95). In retrospect, these inconsistent findings are not surprising because the measured vascular responses are influenced by the experimental preparation, the nature and intensity of the vasoconstrictor stimulus, as well as the mode, intensity, and duration of the exercise stimulus.…”

“…At present, neither adenosine nor prostaglandins appear to be obligatory for functional sympatholysis (20,34,69,90,93). In contrast, a study in humans has implicated local tissue hypoxia as an important factor in the attenuated vasoconstrictor response to SNA in exercising muscle (34).…”

“…However, the smaller relative decrease in conductance in exercising muscle leads to the opposite conclusion! To directly address the influence of vasodilation and elevated blood flow per se on sympathetic responsiveness, some investigators have administered vasodilator stimuli in resting muscle to match the increases in blood flow induced by exercise (20,68,86,87,93,95). These important control experiments have consistently shown that, as baseline diameter, flow, or conductance increases in resting muscle (via graded vasodilator administration), the vasoconstrictor response to sympathetic activation is either enhanced (absolute response) or unchanged (relative response).…”

Too Much Is Not Enough

“…Third, all of these changes occur in a finely regulated way that balances the "demands" of the active muscles for blood flow and oxygen with the need to regulate MAP. 2,6,8 In fact, it might be argued that the "goal" of multiple redundant "collaborating" but sometimes "competing" physiological responses is maintenance of a fine balance among cardiac output, skeletal muscle blood flow, and a "reasonable" and tightly regulated MAP.…”

“…1,2 This is caused by marked metabolic vasodilation along with a local metabolite-mediated blunting of ␣-adrenergic vasoconstriction (functional sympatholysis) in the active muscles. [5][6][7] Thus, diastolic pressure either remains relatively constant or can even fall dramatically in the athletes mentioned above. This means that whereas systolic pressure and pulse pressure both increase, the net effect on MAP is either modest or minimal.…”