GABAergic mechanisms involved in the vagally mediated heart rate response to muscle contraction as revealed by studies with benzodiazepines

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.