title: Stress-associated cardiovascular reaction masks heart rate dependence on physical load in mice.
abstract: When tested on the treadmill mice do not display a graded increase of heart rate (HR), but rather a sharp shift of cardiovascular indices to high levels at the onset of locomotion. We hypothesized that under test conditions cardiovascular reaction to physical load in mice is masked with stress-associated HR increase. To test this hypothesis we monitored mean arterial pressure (MAP) and heart rate in C57BL/6 mice after exposure to stressful stimuli, during spontaneous locomotion in the open-field test, treadmill running or running in a wheel installed in the home cage. Mice were treated with β1-adrenoblocker atenolol (2mg/kg ip, A), cholinolytic ipratropium bromide (2mg/kg ip, I), combination of blockers (A+I), anxiolytic diazepam (5mg/kg ip, D) or saline (control trials, SAL). MAP and HR in mice increased sharply after handling, despite 3weeks of habituation to the procedure. Under stressful conditions of open field test cardiovascular parameters in mice were elevated and did not depend on movement speed. HR values did not differ in I and SAL groups and were reduced with A or A+I. HR was lower at rest in D pretreated mice. In the treadmill test HR increase over speeds of 6, 12 and 18m/min was roughly 1/7-1/10 of HR increase observed after placing the mice on the treadmill. HR could not be increased with cholinolytic (I), but was reduced after sympatholytic (A) or A+I treatment. Anxiolytic (D) reduced heart rate at lower speeds of movement and its overall effect was to unmask the dependency of HR on running speed. During voluntary running in non-stressful conditions of the home cage HR in mice linearly increased with increasing running speeds. We conclude that in test situations cardiovascular reactions in mice are governed predominantly by stress-associated sympathetic activation, rendering efforts to evaluate HR and MAP reactions to workload unreliable.
authors.affiliation: Institute of Biomedical Problems, Russian Academy of Sciences, Moscow 123007, 76A Khoroshevskoe Shosse, Russia; Lomonosov Moscow State University, Biology Faculty, Moscow 119234, 1/12 Leninskie Gory, Russia. Electronic address: aandrievsky@gmail.com.
authors.forename: A A
authors.initials: AA
authors.lastname: Andreev-Andrievskiy
authors.affiliation: Institute of Biomedical Problems, Russian Academy of Sciences, Moscow 123007, 76A Khoroshevskoe Shosse, Russia; Lomonosov Moscow State University, Biology Faculty, Moscow 119234, 1/12 Leninskie Gory, Russia.
authors.forename: A S
authors.initials: AS
authors.lastname: Popova
authors.affiliation: Institute of Biomedical Problems, Russian Academy of Sciences, Moscow 123007, 76A Khoroshevskoe Shosse, Russia.
authors.forename: A S
authors.initials: AS
authors.lastname: Borovik
authors.affiliation: Anokhin Institute of Normal Physiology, Russian Academy of Medical Sciences, Moscow 125009, 11/4 Mokhovaya St, Russia.
authors.forename: O N
authors.initials: ON
authors.lastname: Dolgov
authors.affiliation: Institute of Biomedical Problems, Russian Academy of Sciences, Moscow 123007, 76A Khoroshevskoe Shosse, Russia.
authors.forename: D V
authors.initials: DV
authors.lastname: Tsvirkun
authors.affiliation: University of Angers, Rue Haute de Reculée, 49045 Angers Cedex 01, France.
authors.forename: M
authors.initials: M
authors.lastname: Custaud
authors.affiliation: Institute of Biomedical Problems, Russian Academy of Sciences, Moscow 123007, 76A Khoroshevskoe Shosse, Russia.
authors.forename: O L
authors.initials: OL
authors.lastname: Vinogradova
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists; D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001262:Atenolol / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology*; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004338:Drug Combinations; D005080:Exercise Test; D005106:Exploratory Behavior / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D009241:Ipratropium / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010805:Physical Conditioning, Animal / Q000502:physiology*; D013315:Stress, Psychological / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D014151:Anti-Anxiety Agents; D018680:Cholinergic Antagonists; D004338:Drug Combinations; D001262:Atenolol; D009241:Ipratropium; D003975:Diazepam
keywords: Blood pressure; Exercise; Heart rate; Mice; Stress; Telemetry