Characterization of vagal afferent subtypes stimulated by bradykinin in guinea pig trachea.
(17/2742)
In vitro electrophysiological techniques were used to examine the effect of bradykinin on guinea pig trachea and bronchus afferent nerve endings arising from the nodose or jugular ganglia. The data reveal that bradykinin activates nerve terminals of jugular C and Adelta fibers. Although the fibers were too few in number to study rigorously, bradykinin also stimulated nodose C fibers innervating the trachea and bronchus. In contrast, Adelta fibers arising from the nodose ganglion were unresponsive to bradykinin challenge. The responses in both jugular C and Adelta fiber types were blocked by a selective bradykinin B2 receptor antagonist and were not dependent on the efferent release of sensory neuropeptides. These data indicate that the sensitivity of guinea pig airway afferent fibers to bradykinin is dependent more on the ganglionic origin of the cell body than on the conduction velocity of its axon. (+info)
Vagal afferents and active upper airway closure during pulmonary edema in lambs.
(18/2742)
The present study was undertaken to gain further insight into the mechanisms responsible for the sustained active expiratory upper airway closure previously observed during high-permeability pulmonary edema in lambs. The experiments were conducted in nonsedated lambs, in which airflow and thyroarytenoid and inferior pharyngeal constrictor muscle electromyographic activity were recorded. We first studied the consequences of hemodynamic pulmonary edema (induced by impeding pulmonary venous return) on upper airway dynamics in five lambs; under this condition, a sustained expiratory upper airway closure consistently appeared. We then tested whether expiratory upper airway closure was related to vagal afferent activity from bronchopulmonary receptors. Five bivagotomized lambs underwent high-permeability pulmonary edema: no sustained expiratory upper airway closure was observed. Finally, we studied whether a sustained decrease in lung volume induced a sustained expiratory upper airway closure. Five lambs underwent a 250-ml pleural infusion: no sustained expiratory upper airway closure was observed. We conclude that 1) the sustained expiratory upper airway closure observed during pulmonary edema in nonsedated lambs is related to stimulation of vagal afferents by an increase in lung water and 2) a decrease in lung volume does not seem to be the causal factor. (+info)
The effects of the hypothalamus on hemodynamic changes elicited by vagal nerve stimulation.
(19/2742)
To investigate the means by which neurogenic shock or syncope occur in dentistry, we determined the hemodynamic response to the activation of vagal tone in cats while they were under emotional stress. The hypothalamus and the vagal nerve were electrically stimulated to produce emotional stress and to activate vagal tone, respectively. Hemodynamic changes were recorded during vagal stimulation (Va group) and during vagal stimulation preceded by hypothalamic stimulation (AH + Va group). Although blood pressure decreased in both groups, the degree of hypotensive response in the AH + Va group was greater than the response in the Va group. Total peripheral resistance (TPR) was reduced in the AH + Va group but was increased in the Va group. The blood flow to the skeletal muscles in the AH + Va group was greater than that of the Va group. Reduced TPR, which could be due to vasodilation in the skeletal muscles, was the cause of intensified hypotension in the AH + Va group. Clearly, the hypotension produced by vagal stimulation was worsened when it was preceded by hypothalamic stimulation; this occurrence could be related to the tendency of blood to flow to the skeletal muscles. (+info)
Antigen-induced hyperreactivity to histamine: role of the vagus nerves and eosinophils.
(20/2742)
M2 muscarinic receptors limit acetylcholine release from the pulmonary parasympathetic nerves. M2 receptors are dysfunctional in antigen-challenged guinea pigs, causing increased vagally mediated bronchoconstriction. Dysfunction of these M2 receptors is due to eosinophil major basic protein, which is an antagonist for M2 receptors. Histamine-induced bronchoconstriction is composed of a vagal reflex in addition to its direct effect on airway smooth muscle. Because hyperreactivity to histamine is seen in antigen-challenged animals, we hypothesized that hyperreactivity to histamine may be due to increased vagally mediated bronchoconstriction caused by dysfunction of M2 receptors. In anesthetized, antigen-challenged guinea pigs, histamine-induced bronchoconstriction was greater than that in control guinea pigs. After vagotomy or atropine treatment, the response to histamine in antigen-challenged animals was the same as that in control animals. In antigen-challenged animals, blockade of eosinophil influx into the airways or neutralization of eosinophil major basic protein prevented the development of hyperreactivity to histamine. Thus hyperreactivity to histamine in antigen-challenged guinea pigs is vagally mediated and dependent on eosinophil major basic protein. (+info)
Human sympathetic and vagal baroreflex responses to sequential nitroprusside and phenylephrine.
(21/2742)
We evaluated a method of baroreflex testing involving sequential intravenous bolus injections of nitroprusside followed by phenylephrine and phenylephrine followed by nitroprusside in 18 healthy men and women, and we drew inferences regarding human sympathetic and vagal baroreflex mechanisms. We recorded the electrocardiogram, photoplethysmographic finger arterial pressure, and peroneal nerve muscle sympathetic activity. We then contrasted least squares linear regression slopes derived from the depressor (nitroprusside) and pressor (phenylephrine) phases with 1) slopes derived from spontaneous fluctuations of systolic arterial pressures and R-R intervals, and 2) baroreflex gain derived from cross-spectral analyses of systolic pressures and R-R intervals. We calculated sympathetic baroreflex gain from integrated muscle sympathetic nerve activity and diastolic pressures. We found that vagal baroreflex slopes are less when arterial pressures are falling than when they are rising and that this hysteresis exists over pressure ranges both below and above baseline levels. Although pharmacological and spontaneous vagal baroreflex responses correlate closely, pharmacological baroreflex slopes tend to be lower than those derived from spontaneous fluctuations. Sympathetic baroreflex slopes are similar when arterial pressure is falling and rising; however, small pressure elevations above baseline silence sympathetic motoneurons. Vagal, but not sympathetic baroreflex gains vary inversely with subjects' ages and their baseline arterial pressures. There is no correlation between sympathetic and vagal baroreflex gains. We recommend repeated sequential nitroprusside followed by phenylephrine doses as a simple, efficientmeans to provoke and characterize human vagal and sympathetic baroreflex responses. (+info)
Electrophysiological and morphological heterogeneity of rat dorsal vagal neurones which project to specific areas of the gastrointestinal tract.
(22/2742)
1. The electrophysiological properties of rat dorsal motor nucleus of the vagus (DMV) neurones (n = 162) were examined using whole cell patch clamp recordings from brainstem slices. Recordings were made from DMV neurones whose projections to the gastrointestinal tract had been identified by previously applying fluorescent retrograde tracers to the gastric fundus, corpus or antrum/pylorus, or to the duodenum or caecum. 2. The neuronal groups were markedly heterogeneous with respect to several electrophysiological properties. For example, neurones which projected to the fundus had a higher input resistance (400 +/- 25 Momega), a smaller and shorter after-hyperpolarization (16.7 +/- 0.49 mV and 63.5 +/- 3.9 ms) and a higher frequency of action potential firing (19.3 +/- 1.4 action potentials s-1) following injection of depolarizing current (270 pA) when compared with caecum-projecting neurones (302 +/- 22 Momega; 23. 5 +/- 0.87 mV and 81.1 +/- 5.3 ms; 9.7 +/- 1.1 action potentials s-1; P < 0.05 for each parameter). Differences between neuronal groups were also apparent with respect to the distribution of several voltage-dependent potassium currents. Inward rectification was present only in caecum-projecting neurones, for example. 3. Neurones (n = 82) were filled with the intracellular stain Neurobiotin allowing post-fixation morphological reconstruction. Neurones projecting to the caecum had the largest cell volume (5238 +/- 535 microm3), soma area (489 +/- 46 microm2) and soma diameter (24.6 +/- 1.24 microm) as well as the largest number of dendritic branch segments (23 +/- 2). 4. In summary, these results suggest that DMV neurones are heterogeneous with respect to some electrophysiological as well as some morphological properties and can be divided into subgroups according to their gastrointestinal projections. (+info)
Autonomic modification of the atrioventricular node during atrial fibrillation: role in the slowing of ventricular rate.
(23/2742)
BACKGROUND: Postganglionic vagal stimulation (PGVS) by short bursts of subthreshold current evokes release of acetylcholine from myocardial nerve terminals. PGVS applied to the atrioventricular node (AVN) slows nodal conduction. However, little is known about the ability of PGVS to control ventricular rate (VR) during atrial fibrillation (AF). METHODS AND RESULTS: To quantify the effects and establish the mechanism of PGVS on the AVN, AF was simulated by random high right atrial pacing in 11 atrial-AVN rabbit heart preparations. Microelectrode recordings of cellular action potentials (APs) were obtained from different AVN regions. Five intensities and 5 modes of PGVS delivery were evaluated. PGVS resulted in cellular hyperpolarization, along with depressed and highly heterogeneous intranodal conduction. Compact nodal AP exhibited decremental amplitude and dV/dt and multiple-hump components, and at high PGVS intensities, a high degree of concealed conduction resulted in a dramatic slowing of the VR. Progressive increase of PGVS intensity and/or rate of delivery showed a significant logarithmic correlation with a decrease in VR (P<0.001). Strong PGVS reduced the mean VR from 234 to 92 bpm (P<0.001). The PGVS effects on the cellular responses and VR during AF were fully reproduced in a model of direct acetylcholine injection into the compact AVN via micropipette. CONCLUSIONS: These studies confirmed that PGVS applied during AF could produce substantial VR slowing because of acetylcholine-induced depression of conduction in the AVN. (+info)
Ganglionic mechanisms contribute to diminished vagal control in heart failure.
(24/2742)
BACKGROUND: Previous work has shown that spontaneous and stimulated vagal activity is diminished in heart failure (HF) despite upregulation of functional postsynaptic cholinergic mechanisms. We therefore examined function of the postganglionic neuron in the paced canine model of HF as a possible site for diminished control. METHODS AND RESULTS: We measured sinus cycle length changes in response to electrical stimulation of preganglionic and postganglionic parasympathetic neurons innervating the sinoatrial node in control and HF dogs (both, n=8). Cervical vagus stimulation (preganglionic) demonstrated attenuated responses in the HF group at all levels of stimulation (P<0.05). Stimulation of the right atrial fat pad, containing both postganglionic nerves and terminals of preganglionic neurons, showed no such difference between control and HF (200+/-25 versus 192+/-18 ms). To ensure that preganglionic input and different levels of baseline sympathetic activity did not contribute to the group difference, similar stimulations were done in the presence of ganglionic and beta-adrenergic blockade. Under these conditions, postganglionic stimulation showed smaller changes in sinus cycle length, but the HF group response remained significantly higher than in controls (76+/-10 versus 20+/-2 ms; P<0. 01), indicating that the difference was independent of preganglionic input and sympathetic activity. CONCLUSIONS: A component of attenuated parasympathetic control in HF is located within the peripheral efferent limb. This defect is located within the parasympathetic ganglion. Future work should be focused on determining mechanisms of attenuated ganglionic transmission so that means targeted at restoring vagal activity can be developed. (+info)