Exercise intensity‐dependent contribution of β‐adrenergic receptor‐mediated vasodilatation in hypoxic humans

Abstract

We previously reported that hypoxia-mediated reductions in α-adrenoceptor sensitivity do not explain the augmented vasodilatation during hypoxic exercise, suggesting an enhanced vasodilator signal. We hypothesized that β-adrenoceptor activation contributes to augmented hypoxic exercise vasodilatation. Fourteen subjects (age: 29 ± 2 years) breathed hypoxic gas to titrate arterial O 2 saturation (pulse oximetry) to 80%, while remaining normocapnic via a rebreath system. Brachial artery and antecubital vein catheters were placed in the exercising arm. Under normoxic and hypoxic conditions, baseline and incremental forearm exercise (10% and 20% of maximum) was performed during control (saline), α-adrenoceptor inhibition (phentolamine), and combined α-and β-adrenoceptor inhibition (phentolomine/propranolol). Forearm blood flow (FBF), heart rate, blood pressure, minute ventilation, and end-tidal CO 2 were determined. Hypoxia increased heart rate (P < 0.05) and minute ventilation (P < 0.05) at rest and exercise under all drug infusions, whereas mean arterial pressure was unchanged. Arterial adrenaline (P < 0.05) and venous noradrenaline (P < 0.05) were higher with hypoxia during all drug infusions. The change (Δ) in FBF during 10% hypoxic exercise was greater with phentolamine (Δ306 ± 43 ml min −1 ) vs. saline (Δ169 ± 30 ml min −1 ) or combined phentolamine/propranolol (Δ213 ± 25 ml min −1 ; P < 0.05 for both). During 20% hypoxic exercise, ΔFBF was greater with phentalomine (Δ466 ± 57 ml min −1 ; P < 0.05) vs. saline (Δ346 ± 40 ml min −1 ) but was similar to combined phentolamine/propranolol (Δ450 ± 43 ml min −1 ). Thus, in the absence of overlying vasoconstriction, the contribution of β-adrenergic mechanisms to the augmented hypoxic vasodilatation is dependent on exercise intensity.

Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs

“…Adenosine appears to contribute only during hypoperfusion (75,83). ␤-Adrenergic receptor mechanisms appear to contribute during lower intensity hypoxic exercise (509), but much of this contribution is likely due to ␤-adrenergic-mediated NO release (73,117). This response again highlights the general observation that many dilator substances involved in exercise hyperemia have effects both on vascular smooth muscle and the vascular endothelium.…”

“…As discussed earlier, muscle blood flow is augmented during exercise under hypoxic conditions. This augmentation occurs despite an increase in sympathetic vasoconstrictor activity directed at the skeletal muscle (196), which is capable of restraining the increase in blood flow to the contracting muscle during hypoxia (456,509). So there is competition between hypoxic dilation and sympathetic constriction and evidence that hypoxia can attenuate vasoconstrictor responses to sympathetic nerve activation and exogenous norepinephrine in resting skeletal muscle of animals and humans (48,205,206).…”

Nitric oxide-mediated vasodilation becomes independent of β-adrenergic receptor activation with increased intensity of hypoxic exercise

“…A self-regulating partial rebreathe system that clamps end-tidal CO2 at baseline levels despite large changes in minute ventilation was used to generate hypoxic conditions (1,29,31,32). The target arterial O 2 saturation (SO2; assessed via pulse oximetry) was ϳ80%.…”

“…Previous studies have demonstrated that ␤-adrenergic receptor activation is responsible for a substantial portion of the hypoxic vasodilation at rest (2,29,31) and during mild forearm exercise (31). However, the ␤-adrenergic component of the compensatory vasodilation decreases with increased exercise intensity.…”

“…The combination of these conditions produces a compensatory vasodilation relative to the same level of exercise under normoxic conditions and greater than that predicted by a simple summation of the individual responses (3,5,6,21,23,31,32). The compensatory vasodilation during hypoxic exercise occurs to ensure an adequate oxygen delivery to the active muscles.…”