Norepinephrine transporter inhibition alters the hemodynamic response to hypergravitation.
Sympathetically mediated tachycardia and vasoconstriction maintain blood pressure during hypergravitational stress, thereby preventing gravitation-induced loss of consciousness. Norepinephrine transporter (NET) inhibition prevents neurally mediated (pre)syncope during gravitational stress imposed by head-up tilt testing. Thus it seems reasonable that NET inhibition could increase tolerance to hypergravitational stress. We performed a double-blind, randomized, placebo-controlled crossover study in 11 healthy men (26 +/- 1 yr, body mass index 24 +/- 1 kg/m2), who ingested the selective NET inhibitor reboxetine (4 mg) or matching placebo 25, 13, and 1 h before testing on separate days. We monitored heart rate, blood pressure, and thoracic impedance in three different body positions (supine, seated, standing) and during a graded centrifuge run (incremental steps of 0.5 g for 3 min each, up to a maximal vertical acceleration load of 3 g). NET inhibition increased supine blood pressure and heart rate. With placebo, blood pressure increased in the seated position and was well maintained during standing. However, with NET inhibition, blood pressure decreased in the seated and standing position. During hypergravitation, blood pressure increased in a graded fashion with placebo. With NET inhibition, the increase in blood pressure during hypergravitation was profoundly diminished. Conversely, the tachycardic responses to sitting, standing, and hypergravitation all were greatly increased with NET inhibition. In contrast to our expectation, short-term NET inhibition did not improve tolerance to hypergravitation. Redistribution of sympathetic activity to the heart or changes in baroreflex responses could explain the excessive tachycardia that we observed.
Strempel
Sebastian
S
Franz-Volhard Clinical Research Center, Medical University Charité, Campus Buch, Wiltbergstrasse 50, Haus 129, Berlin, Germany.
Schroeder
Christoph
C
Hemmersbach
Ruth
R
Boese
Andrea
A
Tank
Jens
J
Diedrich
André
A
Heer
Martina
M
Luft
Friedrich C
FC
Jordan
Jens
J
D000222:Adaptation, Physiological; D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002498:Centrifugation; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D018471:Hypergravity / Q000009:adverse effects*; D008297:Male; D009025:Morpholines / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D011187:Posture; D000077593:Reboxetine; D016683:Supine Position; D013610:Tachycardia / Q000209:etiology / Q000503:physiopathology; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D018759:Adrenergic Uptake Inhibitors; D009025:Morpholines; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; D000077593:Reboxetine; D009638:Norepinephrine; D004837:Epinephrine