We explored in 43 healthy subjects the afferent mechanisms of the initial heart rate response to standing by comparing free standing, 70 degrees head-up tilt, handgrip, and contraction of abdominal and leg muscles. The results indicate the following. 1) Standing evokes an immediate, large, bimodal increase of heart rate (HR) of about 20 s duration that far exceeds the gradual HR rise induced by 70 degrees head-up tilt. 2) The immediate HR increase with active standing is due to the exercise reflex and results in a first peak about 3 s after standing briskly. 3) The secondary, more gradual HR increase after 5 s of standing and the subsequent rapid decrease of HR between about 12 and 20 s corresponds through the baroreceptor reflex with a striking fall, recovery, and sometimes overshoot of arterial pressure. 4) The maximum HR increase found after about 12 s of standing is augmented and delayed after rest. 5) The time course of the initial HR response is not modified by physical training. We conclude that active and passive changes of posture result in fundamentally different cardiovascular effects for about 20 s and that "central command," muscle receptors, high-pressure receptors, low-pressure receptors, and the plasma catecholamine level are probably all involved in the initial HR response to standing.

Neurons within the intact respiratory network produce bursts of action potentials that cause inspiration or expiration. Within inspiratory bursts, activity is synchronized on a shorter timescale to generate clusters of action potentials that occur in a set frequency range and are called synchronous oscillations. We investigated how GABA and glycine modulate synchronous oscillations and respiratory rhythm during postnatal development. We recorded inspiratory activity from hypoglossal nerves using the in vitro rhythmically active mouse medullary slice preparation from P0-P11 mice. Average oscillation frequency increased with postnatal development, from 17 +/- 12 Hz in P0-P6 mice (n = 15) to 38 +/- 7 Hz in P7-P11 mice (n = 37) (P < 0.0001). Bath application of GABAA and GlyR antagonists significantly reduced oscillation power in neonates (P0-P6) and juveniles (P7-P10) and increased peak integrated activity in both age groups. To test whether elevating slice excitability is sufficient to reduce oscillation power, Substance P was bath applied alone. Substance P, although increasing peak integrated activity, had no significant effect on oscillation power. Prolonging the time course of GABAergic synaptic currents with zolpidem decreased the median oscillation frequency in P9-P10 mouse slices. These data demonstrate that oscillation frequency increases with postnatal development and that both GABAergic and glycinergic transmission contribute to synchronization of activity. Further, the time course of synaptic GABAergic currents is a determinant of oscillation frequency.

Activin, a member of the transforming growth factor-β family, exerts multiple functions in the nervous system. Originally identified as a neurotrophic and -protective agent, increasing evidence implicates activin also in the regulation of glutamatergic and GABAergic neurotransmission in brain regions associated with cognitive and affective functions. To explore how activin impacts on ethanol potentiation of GABA synapses and related behavioral paradigms, we used an established transgenic model of disrupted activin receptor signaling, in which mice express a dominant-negative activin receptor IB mutant (dnActRIB) under the control of the CaMKIIα promoter. Comparison of GABA A receptor currents in hippocampal neurons from dnActRIB mice and wild-type mice showed that all concentrations of ethanol tested (30-150 mM) produced much stronger potentiation of phasic inhibition in the mutant preparation. In dentate granule cells of dnActRIB mice, tonic GABA inhibition was more pronounced than in wild-type neurons, but remained insensitive to low ethanol (30 mM) in both preparations. The heightened ethanol sensitivity of phasic inhibition in mutant hippocampi resulted from both pre-and postsynaptic mechanisms, the latter probably involving PKCε. At the behavioral level, ethanol produced significantly stronger sedation in dnActRIB mice than in wild-type mice, but did not affect consumption of ethanol or escalation after withdrawal. We link the abnormal narcotic response of dnActRIB mice to ethanol to the excessive potentiation of inhibitory neurotransmission. Our study suggests that activin counteracts oversedation from ethanol by curtailing its augmenting effect at GABA synapses.

Sympathetic stimulation and catecholamine exposure have been shown to sensitize the arterial baroreceptors, but the extent or importance of this effect is not known. We performed this study to investigate the effects of sympathetic feedback on the carotid sinus baroreceptors, specifically examining the effect of the stimulation on the two different functional types of baroreceptors characterized in an earlier study. The existence of two baroreceptor function-response curves has suggested that the roles of the two functionally different baroreceptors may not be the same. If true, the effects of epinephrine exposure on baroreceptor firing characteristics may contribute to differential roles played by each baroreceptor type in the control of blood pressure. Single-fiber baroreceptor activity from a vascularly isolated carotid sinus was recorded during slow increases in carotid sinus pressure before and during exposure to epinephrine (10(-8) to 10(-6) M). Baroreceptor firing characteristics were determined from function curves plotting carotid sinus pressure versus nerve activity, with curve-fitting analysis of the hyperbolic type I and sigmoidal type II baroreceptor curves used to obtain threshold (Pth) and saturation (Psat) pressures, threshold (Fth) and saturation (Fsat) firing rates, and sensitivity (slope) for each baroreceptor before and during epinephrine exposure. The possible mechanisms of observed changes were examined using our previously published baroreceptor computer model. Epinephrine exposure was found to significantly increase sensitivity, Fth, and Fsat of both types of baroreceptors, with a relatively greater effect on type I sensitivity and on type II Fth and Fsat. Epinephrine also was found to increase the level of spontaneous discharge for type II baroreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)