title: GABAergic mechanisms involved in the vagally mediated heart rate response to muscle contraction as revealed by studies with benzodiazepines.
abstract: The aim of this study was to determine if central GABA mechanisms are involved in the cardiac vagal withdrawal at the beginning of exercise in man. We tested whether GABA-enhancing effects of a benzodiazepine could be observed in the HR change (R-R interval) immediately following the onset of a brief (10s) isometric contraction (60 % maximum) of the biceps muscle. The difference between the change in R-R interval occurring during the same phase of respiration was compared for placebo (Pla) and 10 mg oral diazepam (Dz) treatment in a double blind, crossover trial. ECG, blood pressure, respiration and biceps muscle tension were recorded. The subjects breathed to a metronome and R-R interval measurements were plotted for early and late inspiration and early and late expiration. The mean values of the first late expiration R-R interval immediately following the start of contraction in early expiration were compared to the same measurements without contraction. Contractions initiated following diazepam treatment resulted in a significantly greater reduction in R-R interval (P < 0.05) implying that GABAergic suppression of cardiac vagal outflow may be responsible for contraction-induced tachycardia in man.
authors.affiliation: Department of Physiology, The Medical School, The University of Birmingham, Birmingham B15 2TT UK.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Farmer
authors.forename: Hamish F
authors.initials: HF
authors.lastname: Ross
authors.forename: Saqib
authors.initials: S
authors.lastname: Chowdhary
authors.forename: Faisal
authors.initials: F
authors.lastname: Osman
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Townend
authors.forename: John H
authors.initials: JH
authors.lastname: Coote
mesh_terms: D000293:Adolescent; D000328:Adult; D001569:Benzodiazepines; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D003975:Diazepam; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D015444:Exercise / Q000502:physiology; D005260:Female; D018757:GABA Modulators; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007537:Isometric Contraction / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D015656:Respiratory Mechanics / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D018757:GABA Modulators; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid; D003975:Diazepam