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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.

Continuous infusion of lipopolysaccharide (LPS) into conscious rats elicits regionally selective cardiovascular disturbances. The aim of the present study was to assess contractile function in different vascular preparations (renal, mesenteric, and thoracic aorta) taken from rats infused with LPS for 2 or 24 h. Sustained responses to continuous infusion of methoxamine but not to KCl were reduced in the aorta (at 2 and 24 h LPS) and mesentery (at 24 h LPS) but not in the renal vascular bed. In contrast, transient responses to bolus doses of methoxamine were unchanged in the mesentery. In Ca 2ϩ -imaging experiments with fura-2, challenge with a single concentration of methoxamine (10 M, which showed an impaired contractile response at 24 h LPS) induced a rise in intracellular Ca 2ϩ in the mesenteric artery that was not different from the control. Furthermore, in the aorta, the contractile response to caffeine was attenuated only in the 2 h LPS group. These results show that there is regional heterogeneity in in vitro vascular responsiveness in preparations taken from LPS-infused rats. Thus, in mesenteric beds and aortae, but not renal beds, there is hypocontractility to methoxamine that is not due to a generalized inability of the smooth muscle to contract, which is evident with sustained but not transient application of agonist (mesentery) and which, in late endotoxemia (24 h LPS), does not appear to involve abnormalities in Ca 2ϩ mobilization or entry.