title: Differential effects of low- and high-intensity lower body negative pressure on noradrenaline and adrenaline kinetics in humans.
abstract: 1. Lower body negative pressure provides a means to examine neurocirculatory reflexive responses to decreases in venous return to the heart. We assessed whether the pattern of catecholaminergic responses to lower body negative pressure depends on the intensity of the stimulus (-15 versus -40 mmHg). 2. In 14 healthy subjects, responses of forearm blood flow and noradrenaline spillover and of total body noradrenaline and adrenaline spillover were assessed during infusion of [3H]noradrenaline and [3H]adrenaline during -15 and -40 mmHg of lower body negative pressure. 3. During lower body negative pressure at -15 mmHg, heart rate and pulse pressure did not change, but forearm vascular resistance increased by 25-50%. Forearm noradrenaline spillover increased by about 50%, from 0.63 +/- 0.16 to 0.94 +/- 0.23 pmol min-1 100 ml-1 (P < 0.05). Total body noradrenaline spillover did not change, and total body adrenaline spillover increased significantly by about 30%. Clearances of noradrenaline and adrenaline were unchanged. 4. During lower body negative pressure at -40 mmHg, heart rate increased and pulse pressure decreased. Forearm vascular resistance increased by about 100%, and forearm noradrenaline spillover increased by 80%, from 0.73 +/- 0.19 to 1.32 +/- 0.36 pmol min-1 100 ml-1 (P < 0.05). Total body noradrenaline spillover increased by 30%, and total body adrenaline spillover increased by about 50%. Clearances of both noradrenaline and adrenaline decreased. 5. The results are consistent with the view that selective deactivation of cardiopulmonary baroreceptors during low-intensity lower body negative pressure increases sympathoneural traffic to forearm skeletal muscle and increases adrenomedullary secretion without a concomitant generalized increase in sympathoneural outflows. Concurrent deactivation of cardiopulmonary and arterial baroreceptors during high-intensity lower body negative pressure evokes a more generalized increase in sympathoneural activity, accompanied by further increased adrenomedullary secretion and decreased plasma clearances of noradrenaline and adrenaline. The findings support differential increases in skeletal sympathoneural and adrenomedullary outflows during orthostasis, with more generalized sympathoneural responses to systemic hypotension.
authors.affiliation: Department of Medicine, St. Radboud University Hospital, Nijmegen, Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Jacobs
authors.forename: D S
authors.initials: DS
authors.lastname: Goldstein
authors.forename: J J
authors.initials: JJ
authors.lastname: Willemsen
authors.forename: P
authors.initials: P
authors.lastname: Smits
authors.forename: T
authors.initials: T
authors.lastname: Thien
authors.forename: J W
authors.initials: JW
authors.lastname: Lenders
mesh_terms: D000328:Adult; D017704:Baroreflex / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D004837:Epinephrine / Q000097:blood / Q000493:pharmacokinetics*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008150:Lower Body Negative Pressure; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000493:pharmacokinetics*; D012039:Regional Blood Flow / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D009638:Norepinephrine; D004837:Epinephrine