title: 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.
authors.affiliation: Division of Cardiology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
authors.forename: U
authors.initials: U
authors.lastname: Leuenberger
authors.forename: K
authors.initials: K
authors.lastname: Gleeson
authors.forename: K
authors.initials: K
authors.lastname: Wroblewski
authors.forename: S
authors.initials: S
authors.lastname: Prophet
authors.forename: R
authors.initials: R
authors.lastname: Zelis
authors.forename: C
authors.initials: C
authors.lastname: Zwillich
authors.forename: L
authors.initials: L
authors.lastname: Sinoway
mesh_terms: D000328:Adult; D001794:Blood Pressure; D005542:Forearm / Q000098:blood supply; D006339:Heart Rate; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D009132:Muscles / Q000098:blood supply; D009638:Norepinephrine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D010108:Oxyhemoglobins / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000502:physiology / Q000503:physiopathology; D014655:Vascular Resistance
chemical_list: D010108:Oxyhemoglobins; D009638:Norepinephrine