Hypoxemia raises muscle sympathetic activity but not norepinephrine in resting humans

Abstract

The experimental objective was to determine whether moderate to severe hypoxemia increases skeletal muscle sympathetic nervous activity (MSNA) in resting humans without increasing venous plasma concentrations of norepinephrine (NE) and epinephrine (E). In nine healthy subjects (20-34 yr), we measured MSNA (peroneal nerve), venous plasma levels of NE and E, arterial blood pressure, heart rate, and end-tidal O2 and CO2 before (control) and during breathing of 1) 12% O2 for 20 min, 2) 10% O2 for 20 min, and 3) 8% O2 for 10 min--in random order. MSNA increased above control in five, six, and all nine subjects during 12, 10, and 8% O2, respectively (P less than 0.01), but only after delays of 12 (12% O2) and 4 min (8 and 10% O2). MSNA (total activity) rose 83 +/- 20, 260 +/- 146, and 298 +/- 109% (SE) above control by the final minute of breathing 12, 10, and 8% O2, respectively. NE did not rise above control at any level of hypoxemia; E rose slightly (P less than 0.05) at one time only with both 10 and 8% O2. Individual changes in MSNA during hypoxemia were unrelated to elevations in heart rate or decrements in blood pressure and end-tidal CO2--neither of which always fell. We conclude that in contrast to some other sympathoexcitatory stimuli such as exercise or cold stress, moderate to severe hypoxemia increases leg MSNA without raising plasma NE in resting humans.

Sympathetic activity is influenced by task difficulty and stress perception during mental challenge in humans.

“…Moreover, greater elevations in MSNA than observed here might be anticipated. Compared to other physiological stimuli such as cold (Victor, Leimbach, Seals, Wallin & Mark, 1987; Seals, 1990), exercise (Mark, Victor, Nerhed & Wallin, 1985;Seals et al 1988), or hypoxia (Saito, Mano, Iwase, Koga, Abe & Yamazaki, 1988;Rowell, Johnson, Chase, Comess & Seals, 1989), which may stimulate MSNA more directly and with greater consistency among subjects, the level of MSNA excitation observed during mental stress is relatively weak.…”

Augmented Sympathetic Activation During Short-Term Hypoxia and High-Altitude Exposure in Subjects Susceptible to High-Altitude Pulmonary Edema

“…Our findings in HAPE-resistant subjects are consistent with earlier data showing that mild, short-term hypoxia causes little or no sympathetic activation in normal subjects. 15,28 Finally, the exaggerated sympathetic responsiveness in HAPE-prone subjects appears to be specific for hypoxia (as evidenced by the normal responses to the cold pressor test and the Valsalva maneuver). It should be noted that in these studies, we measured sympathetic outflow targeted at the skeletal vasculature.…”

“…11,12 In humans, plasma catecholamines, indirect markers of sympathetic activity, remained unchanged during shortterm hypoxia but increased in some, but not other, studies during prolonged exposure to high altitude. [13][14][15][16][17] In studies using direct microneurographic measurements of muscle sympathetic nerve activity (MSNA) in humans, brief and/or mild hypoxia caused little or no change in MSNA, whereas more sustained and severe hypoxia rather consistently stimulated sympathetic activity. 15,16,18,19 Part of the discrepancy between norepinephrine plasma concentration and MSNA findings in these human studies could be related to the stimulation of norepinephrine clearance by hypoxia.…”

“…[13][14][15][16][17] In studies using direct microneurographic measurements of muscle sympathetic nerve activity (MSNA) in humans, brief and/or mild hypoxia caused little or no change in MSNA, whereas more sustained and severe hypoxia rather consistently stimulated sympathetic activity. 15,16,18,19 Part of the discrepancy between norepinephrine plasma concentration and MSNA findings in these human studies could be related to the stimulation of norepinephrine clearance by hypoxia. 20 Thus, although there is evidence that hypoxia stimulates postganglionic sympathetic nerve activity in humans, no data are available at high altitude and in HAPE-susceptible subjects.…”

Chronic hypoxia increases blood pressure and noradrenaline spillover in healthy humans

“…Hypoxia-mediated sympathetic activation is currently envisaged as a defence mechanism to assure O 2 supply to critical organs by means of raising cardiac output and regulating regional conductances (Rowell et al 1989;Leuenberger et al 1991;Duplain et al 1999;Calbet, 2000). In contrast, hypoxia either directly, or through its metabolic effects, causes vasodilatation in most vascular beds, such that sympathetic tone should be increased to avoid exaggerated vasodilatation and hypotension (Hilton & Eichholtz, 1925;Rowell et al 1989;Laughlin et al 1996). Elevated sympathetic activity has also been reported in patients with chronic hypoxaemia (defined as a low arterial pressure of O 2 (P a, J)) (Heindl et al 2001), as well as in patients with sleep apnoea who are intermittently hypoxaemic (Imadojemu et al 2002).…”