title: Human muscle sympathetic activity and cardiac catecholamine spillover: no support for augmented sympathetic noradrenaline release by adrenaline co-transmission.
abstract: 1. Evidence from animal studies indicates that circulating adrenaline may be taken up into sympathetic nerves, facilitating the release of noradrenaline. To test whether adrenaline acts as a co-transmitter in humans we studied eight healthy men (aged 19-23 years) during isometric handgrip before and after an adrenaline infusion (1-3 micrograms/min for > 30 min). Sympathetic activity was assessed using radiotracer kinetic techniques to measure total and cardiac spillovers of noradrenaline and adrenaline, and microneurography to measure muscle sympathetic activity. 2. During the adrenaline infusion systolic blood pressure and heart rate increased significantly and diastolic blood pressure decreased. Total noradrenaline spillover, and arterial and coronary sinus plasma noradrenaline concentrations, increased significantly. Muscle sympathetic nerve traffic increased both during and after the end of the infusion. 3. Thirty minutes after the end of the adrenaline infusion there was adrenaline release from the heart (1.5 +/- 0.4 ng/min, mean +/- S.E.M.) indicating that significant adrenaline loading of cardiac sympathetic nerves had occurred. At this time muscle sympathetic nerve traffic and total body and cardiac noradrenaline spillovers were similar (P > 0.05) to pre-adrenaline infusion values (nerve traffic 24 +/- 4 versus 21 +/- 3 bursts/min; total noradrenaline spillover 698 +/- 98 versus 618 +/- 119 ng/min; cardiac noradrenaline spillover 16.2 +/- 2.8 versus 13.9 +/- 3.9 ng/min). 4. Isometric handgrip contraction evoked similar responses pre- and post-adrenaline infusion in total and cardiac noradrenaline spillovers and in muscle sympathetic activity. 5. The results do not support the theory that adrenaline is a co-transmitter facilitating noradrenaline release from human sympathetic nerves.
authors.affiliation: Alfred Baker Medical Unit, Alfred Hospital, Prahran, Victoria, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Thompson
authors.forename: B G
authors.initials: BG
authors.lastname: Wallin
authors.forename: G W
authors.initials: GW
authors.lastname: Lambert
authors.forename: G L
authors.initials: GL
authors.lastname: Jennings
authors.forename: M D
authors.initials: MD
authors.lastname: Esler
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004837:Epinephrine / Q000008:administration & dosage / Q000378:metabolism*; D006225:Hand; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D013566:Sympathomimetics / Q000008:administration & dosage / Q000378:metabolism*; D013997:Time Factors
chemical_list: D013566:Sympathomimetics; D009638:Norepinephrine; D004837:Epinephrine