Norepinephrine clearance is increased during acute hypoxemia in humans

Abstract

Acute hypoxemia leads to activation of the sympathetic nervous system (SNS), yet adrenergic vasoconstriction does not occur and venous plasma norepinephrine (NE) fails to rise as expected. To examine whether this dissociation between SNS tone and plasma NE is due to altered metabolism of NE, we measured arterial NE kinetics ([3H]NE infusion technique) and sympathetic nervous outflow to muscle (peroneal microneurography) during 25-30 min of hypoxemia (spontaneous breathing, mean O2 saturation 74%) in six healthy young men. During hypoxemia, muscle sympathetic nervous activity (MSNA) rose significantly from 12.2 +/- 3.3 to 18.6 +/- 3.5 bursts/min, and the total amplitude increased from 123 +/- 36 to 255 +/- 50 mm/min. NE spillover, an index of NE release at the sympathetic nerve terminals, rose from 1.66 +/- 0.30 to 2.33 +/- 0.40 nmol.min-1.m-2 (P = 0.014). However, NE clearance increased also from 0.99 +/- 0.05 to 1.19 +/- 0.11 l.min-1.m-2 (P = 0.014), and arterial NE rose from 281 +/- 50 to 339 +/- 64 pg/ml (P = 0.023). Hypoxemia resulted in a significant rise in forearm blood flow and a decrease in forearm vascular resistance. The fact that skin blood flow and vascular resistance did not change implies that forearm vasodilation was localized to skeletal muscle. Our results suggest that during acute hypoxemia in humans the SNS is activated but the rise in plasma NE is attenuated because NE clearance is increased.

Chronic hypoxia increases blood pressure and noradrenaline spillover in healthy humans

“…Following 20-30 min acute exposure to a level of hypoxia of similar magnitude to that used in the present study, NA spillover was increased by 46 % while NA clearance was reduced by 20 % (Leuenberger et al 1991). The present study indicates that altitude acclimatisation results in a restoration of sea level NA clearance while spillover is remarkably elevated, reaching values similar to those reported, for example, in patients with compensated chronic heart failure (Azevedo et al 2000).…”

“…A less accentuated elevation in NA spillover has been reported in acute hypoxia (Leuenberger et al 1991). Following 20-30 min acute exposure to a level of hypoxia of similar magnitude to that used in the present study, NA spillover was increased by 46 % while NA clearance was reduced by 20 % (Leuenberger et al 1991).…”

“…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).…”

Systemic Hypoxia Elevates Skeletal Muscle Interstitial Adenosine Levels in Humans

“…It is well documented that during systemic hypoxia, peripheral blood flow is increased. 1,3 In the present study, FBF was determined in 3 subjects to confirm this finding. It was observed that skeletal muscle blood flow was increased 1.3 mL ⅐ min Ϫ1 ⅐ 100 mL Ϫ1 , whereas in a study by Leuenberger et al 3 using exactly the same protocol, FBF was increased 1.2 mL ⅐ min Ϫ1 ⅐ 100 mL…”

“…To compensate for the decreased O 2 delivery to tissues, a number of mechanisms are activated, resulting in an increase in ventilation, heart rate, cardiac output, and peripheral (muscle) blood flow. [1][2][3] Although a number of different compounds have been suggested to be responsible for the hypoxia-induced increase in blood flow, the most widely recognized and investigated has been adenosine. Much of the previous work has used various heart models, 4 -6 and most of the evidence for a role of adenosine came from studies showing that hypoxia-induced hyperemia was attenuated by adenosine deaminase, 7 adenosine receptor blockade, 4 or the inhibition of adenosine production.…”