心力衰竭状态下的动脉压力感受器反射

心力衰竭是以心脏泵血功能降低（心输出量减少）为始动因素的临床综合征。心输出量降低首先引起动脉压力感受性反射失负荷,进而通过迷走-交感机制加快心率;同时,支配血管床的交感传出活动增强,进而增加总外周阻力。本文主要论述在心力衰竭状态下压力感受性反射在循环功能异常调控中的作用机制。本综述及我们近年的研究表明：（1）在心力衰竭状态下压力感受性反射功能明显减弱;（2）中枢血管紧张素Ⅱ和活性氧在压力感受性反射功能失调中发挥关键作用;（3）心交感传入刺激和化学感受性反射能抑制压力感受性反射;（4）适当的运动可以部分纠正异常的心血管反射活动。     

Functional Organization of Brain Pathways Subserving the Baroreceptor Reflex: Studies in Conscious Animals Using Immediate Early Gene Expression

1. This paper reviews studies carried out in our laboratory in which we have used the c-fos functional mapping method, in combination with other methods, to determine the functional organization of central baroreceptor pathways as they operate in the conscious rabbit.2. First, we showed that periods of induced hypertension or hypotension each result in a specific and reproducible pattern of activation of neurons in the brainstem and forebrain. In particular, hypotension (but not hypertension) results in the activation of catecholamine neurons in the medulla and pons and vasopressin-synthesizing neurons in the hypothalamus.3. The activation of medullary cell groups in response to induced hypertension or hypotension in the conscious rabbit is almost entirely dependent on inputs from arterial baroreceptors, while the activation of hypothalamic vasopressin-synthesising neurons in response to hypotension is largely dependent on baroreceptors, although an increase in circulating angiotensin also appears to contribute.4. Discrete groups of neurons in the rostral ventrolateral medulla (RVLM) and A5 area in the pons are the major groups of spinally projecting neurons activated by baroreceptor unloading. In contrast, spinally projecting neurons in the paraventricular nucleus in the hypothalamus appear to be largely unaffected by baroreceptor signals.5. Direct afferent inputs to RVLM neurons in response to increases or decreases in arterial pressure originate primarily from other medullary nuclei, particularly neurons located in the caudal and intermediate levels of the ventrolateral medulla (CVLM and IVLM), as well as in the nucleus tractus solitarius (NTS).6. There is also a direct projection from barosensory neurons in the NTS to the CVLM/IVLM region, which is activated by baroreceptor inputs.7. Collectively, the results of our studies in conscious animals indicate that baroreceptor signals reach all levels of the brain. With regard to the baroreceptor reflex control of sympathetic activity, our studies are consistent with previous studies in anesthetized animals, but in addition reveal other previously unrecognized pathways that also contribute to this reflex regulation.     

Brain-derived neurotrophic factor in arterial baroreceptor pathways: implications for activity-dependent plasticity at baroafferent synapses

Functional characteristics of the arterial baroreceptor reflex change throughout ontogenesis, including perinatal adjustments of the reflex gain and adult resetting during hypertension. However, the cellular mechanisms that underlie these functional changes are not completely understood. Here, we provide evidence that brain-derived neurotrophic factor (BDNF), a neurotrophin with a well-established role in activity-dependent neuronal plasticity, is abundantly expressed in vivo by a large subset of developing and adult rat baroreceptor afferents. Immunoreactivity to BDNF is present in the cell bodies of baroafferent neurons in the nodose ganglion, their central projections in the solitary tract, and terminal-like structures in the lower brainstem nucleus tractus solitarius . Using ELISA in situ combined with electrical field stimulation, we show that native BDNF is released from cultured newborn nodose ganglion neurons in response to patterns that mimic the in vivo activity of baroreceptor afferents. In particular, high-frequency bursting patterns of baroreceptor firing, which are known to evoke plastic changes at baroreceptor synapses, are significantly more effective at releasing BDNF than tonic patterns of the same average frequency. Together, our study indicates that BDNF expressed by first-order baroreceptor neurons is a likely mediator of both developmental and post-developmental modifications at first-order synapses in arterial baroreceptor pathways.     

The role of enzymatic processing in the biological actions of substance P

There is considerable evidence that substance P (SP) is a neurotransmitter in the CNS. Current findings suggest that the effects of synaptically released SP are terminated by enzymatic breakdown, primarily by endopeptidase 3.4.24.11 (endo 24.11). The products of cleavage by endo 24.11 include the amino-terminal fragment SP(1-7). Evidence suggests that SP is involved in mediating baroreceptor reflex activity in the nucleus of the solitary tract (NTS). Microinjection of SP into the NTS lowered blood pressure and heart rate. Microinjection of SP(1-7) into the NTS reproduced the effects of SP on both heart rate and blood pressure. Intra-NTS injection of phosphoramidon, an inhibitor of endo 24.11 activity, completely blocked the effects of a subsequent injection of SP. This blocking effect of phosphoramidon was unaltered by pretreatment with the opiate inhibitor naloxone. In contrast, phosphoramidon failed to block the depressor and bradycardic effects of SP(1-7). The implications of these findings regarding the role of endo 24.11 in the metabolism of SP are discussed.     

Serotonin2 Receptors in the Nucleus Tractus Solitarius: Characterization and Role in the Baroreceptor Reflex Arc

1. There is a general agreement concerning the key role of the baroreceptor reflex in blood pressure homeostasis. It is also well accepted that baroreceptor afferent messages are first integrated within the nucleus tractus solitarius (NTS) and that an excitatory amino acid, probably glutamate, is the principal neurotransmitter of corresponding afferents fibers. However, important points concerning the processing of baroreceptor messages within the NTS remain to be clarified, in particular the possible modulatory role of other neuroactive substances at this particular level in the medulla oblongata.2. In this context, the present review focuses on serotonin, and the possible facilitatory influence of NTS serotonergic afferents and receptors on the baroreceptor reflex arc. Relevant pharmacological, electrophysiological, immunohistochemical, and biochemical data, are presented and discussed. They can be summarized as follows.3. The selective destruction of the nodose ganglion-NTS serotonergic pathway produces a long-term increase in blood pressure variability, similar to that caused by baroreceptor denervation.4. Microinjection of picomolar doses of 5-HT into the NTS elicits the typical responses of baroreceptor activation.5. The cardiovascular effects elicited by local microinjections of specific agonists and antagonists into the NTS of intact rats and of animals that underwent nodose ganglionectomy indicate that the baroreceptor-like effects of locally administered 5-HT are mediated by the activation of postsynaptic 5-HT₂ receptors.6. The medullary pathways which mediate NTS 5-HT₂ receptor-evoked responses are similar to those involved in the baroreceptor reflex arc.7. Pharmacological and electrophysiological studies suggest that the cardiovascular effects of intra-NTS 5-HT involve the 5-HT_2A receptor subtype expressed by NTS barosensitive neurons that receive polysynaptic vagal afferents.8. Intra-NTS microinjection of a subthreshold dose of DOI, a 5-HT₂ receptor agonist, which, on its own, does not produce any cardiovascular changes, significantly enhances the bradycardiac component of the baroreflex.9. Altogether, the data summarized above show that, in the NTS, 5-HT acting at 5-HT_2A receptors exerts a facilitatory influence on the baroreceptor reflex, especially on the cardiac component of this reflex.10. Convergent pharmacological and electrophysiological data indicate that, in the NTS, functional interactions between NMDA- and 5-HT_2A-receptors coexpressed by the same neurons probably underlie the facilitatory influence of 5-HT upon the baroreceptor reflex.11. Under physiological conditions, the 5-HT_2A receptor-mediated facilitatory modulation of the cardiovagal component of the baroreflex might be triggered by 5-HT released from nodose ganglion-NTS serotoninergic afferent neurons and/or for serotoninergic projections originating in raphe nuclei. The latter possibility might notably occur during recovery after physical exercise and/or during the freezing reaction in stressed animals.     

Barosensitive neurons in the rat tractus solitarius and paratrigeminal nucleus: a new model for medullary, cardiovascular reflex regulation

The nucleus of the solitary tract (NTS), a termination site for primary afferent fibers from baroreceptors and other peripheral cardiovascular receptors, contains blood pressure-sensitive neurons, some of which have rhythmic activity locked to the cardiac cycle, making them key components of the central pathway for cardiovascular regulation. The paratrigeminal nucleus (Pa5), a small collection of medullary neurons in the dorsal lateral spinal trigeminal tract, like the NTS, receives primary somatosensory inputs of glossopharyngeal, vagal, and other nerves. Recent studies show that the Pa5 has efferent connections to the rostroventrolateral reticular nucleus (RVL), NTS, and ambiguous nucleus, suggesting that its structure may play a role in the baroreceptor reflex modulation. In the present study, simultaneous recording from multiple single neurons in freely behaving rats challenged with i.v. phenylephrine administration, showed that 83% of NTS units and 72% of Pa5 units were baroreceptor sensitive. Whereas most of the baroreceptor-sensitive NTS and Pa5 neurons (86 and 61%, respectively) increased firing rate during the ascending phase of the pressor response, about 16% of Pa5 and NTS baroreceptor-sensitive neurons had a decreased firing rate. On one hand, the decrease in firing rate occurred during the ascending phase of the pressor response, indicating sensitivity to rapid changes in arterial pressure. On the other hand, the increases in neuron activity in the Pa5 or NTS occurred during the entire pressor response to phenylephrine. Cross-correlational analysis showed that 71% of Pa5 and 93% of NTS baroreceptor-activated neurons possessed phasic discharge patterns locked to the cardiac cycle. These findings suggest that the Pa5, like the NTS, acts as a terminal for primary afferents in the medullary-baroreflex or cardiorespiratory-reflex pathways.     

Glutamate release in midbrain periaqueductal gray by activation of skeletal muscle receptors and arterial baroreceptors

We have previously reported that both skeletal muscle receptor and arterial baroreceptor afferent inputs activate neurons in the dorsolateral (DL) and lateral regions of the midbrain periaqueductal gray (PAG). In this study, we determined whether the excitatory amino acid glutamate (Glu) is released to mediate the increased activity in these regions. Static contraction of the triceps surae muscle for 4 min was evoked by electrical stimulation of the L7 and S1 ventral roots in cats. Activation of arterial baroreceptor was induced by intravenous injection of phenylephrine. The endogenous release of Glu from the PAG was recovered with the use of a microdialysis probe. Glu concentration was measured by the HPLC method. Muscle contraction increased mean arterial pressure (MAP) from 98 +/- 10 to 149 +/- 12 mmHg (P < 0.05) and increased Glu release in the DL and lateral regions of the middle PAG from 0.39 +/- 0.10 to 0.73 +/- 0.12 microM (87%, P < 0.05) in intact cats. After sinoaortic denervation and vagotomy were performed, contraction increased MAP from 95 +/- 12 to 158 +/- 15 mmHg, and Glu from 0.34 +/- 0.08 to 0.54 +/- 0.10 microM (59%, P < 0.05). The increases in arterial pressure and Glu were abolished by muscle paralysis. Phenylephrine increased MAP from 100 +/- 13 to 162 +/- 22 mmHg and increased Glu from 0.36 +/- 0.10 to 0.59 +/- 0.18 microM (64%, P < 0.05) in intact animals. Denervation abolished this Glu increase. Summation of the changes in Glu evoked by muscle receptor and arterial baroreceptor afferent inputs was greater than the increase in Glu produced when both reflexes were activated simultaneously in intact state (123% vs. 87%). These data demonstrate that activation of skeletal muscle receptors evokes release of Glu in the DL and lateral regions of the middle PAG, and convergence of afferent inputs from muscle receptors and arterial baroreceptors in these regions inhibits the release of Glu. These results suggest that the PAG is a neural integrating site for the interaction between the exercise pressor reflex and the arterial baroreceptor reflex.     

Modulation of blood pressure by substance P: opposite effects of N- and C- terminal fragments on anesthetized rats

Considerable evidence suggests that substance P (SP) may be a transmitter mediating the depressor effects of baroreceptor reflex activation within the brainstem, yet intracerebroventricular administration of SP is reported to result in a pronounced pressor effect. In this study, SP injected into the 4th cerebral ventricle produced a biphasic effect; a brief decrease in blood pressure followed by a lengthy increase. Similar injections of a carboxy-terminal fragment of SP produced only a pressor effect of long duration. Injection of an amino-terminal SP fragment produced only a brief, rapid depressor effect. These results suggest that the amino-terminal sequence of SP may be involved in mediating the depressor effects of baroreceptor activation.     

Tonic enhancement of the sensitivity of baroreceptor reflex response by endogenous substance P in the rat.

Modulation of baroreceptor reflex (BRR) by endogenous substance P (SP) in the brain was investigated in rats anesthetized with pentobarbital sodium. Intracerebroventricular administration of the undecapeptide (15 or 30 nmol) and its antagonist, (D-Pro2, D-Trp7,9)-SP (30 or 60 nmol) or SP antiserum (1:20), respectively, promoted a significant increase and decrease in the sensitivity of BRR response. Prolonging the endogenous activity of SP with the aminopeptidase blocker, bestatin (200 nmol) or with the endopeptidase-24.11 inhibitor, phosphoramidon (200 nmol) significantly augmented the same reflex. Combining the undecapeptide with either peptidase blocker, moreover, promoted additional potentiation of the BRR response. On the other hand, simultaneous administration of bestatin and (D-Pro2, D-Trp7,9)-SP produced a reduction of the augmented effect of bestatin on the sensitivity of BRR response. Bilateral microinjection of SP (600 pmol) or an antiserum against SP (1:20) into the nucleus tractus solitarius (NTS) elicited respectively an enhancement of and reduction in the BRR response. These data suggest that neurons that contain SP may participate in central cardiovascular control by tonically enhancing the sensitivity of the BRR response, possibly via an action on the NTS.     

Excitatory convergence of periaqueductal gray and somatic afferents in the solitary tract nucleus: role for neurokinin 1 receptors

Our previous studies (Boscan P, Kasparov S, and Paton JF. Eur J Neurosci 16: 907-920, 2002) showed that activation of somatic afferents attenuated the baroreceptor reflex via neurokinin type 1 (NK(1)) and GABA(A) receptors within the nucleus of the solitary tract (NTS). The periaqueductal gray matter (PAG) can also depress baroreceptor reflex function and project to the NTS. In the present study, we have tested the possibility that the dorsolateral (dl)-PAG projects to the NTS neurons that also respond to somatic afferent input. In an in situ, arterially perfused, unanesthetized decerebrate rat preparation, somatic afferents (brachial plexus), cervical spinal cord, and dl-PAG were stimulated electrically, whereas NTS neurons were recorded extracellularly. From 45 NTS neurons excited by either brachial plexus or dl-PAG stimulation, 41 received convergence excitatory inputs from both afferents. Onset latency and evoked peak discharge frequency from brachial plexus afferents were 39.4 +/- 4.7 ms and 10.7 +/- 1.1 Hz, whereas this was 43.9 +/- 6.4 ms and 7.9 +/- 1 Hz, respectively, following dl-PAG stimulation. As revealed by using a paired pulse stimulation protocol, monosynaptic connections were found in 9 of 36 neurons tested from both spinal cord and dl-PAG. We tested NK(1)-receptor sensitivity in 38 neurons that received convergent inputs from brachial plexus/PAG. Fifteen neurons were sensitive to selective antagonism of NK(1) receptors. CP-99994, the NK(1) antagonist, failed to alter ongoing firing activity but reduced the evoked peak discharge frequency following stimulation of both brachial plexus (from 12.3 +/- 1.8 to 7.2 +/- 1.3 Hz; P < 0.01) and PAG (from 7.8 +/- 1.5 to 4.5 +/- 1 Hz; P < 0.01). We conclude that 1) somatic brachial and PAG afferents can converge onto single NTS neurons; 2) this convergence occurs via either direct or indirect pathways; and 3) NK(1) receptors are activated by some of these inputs.     

腺苷易化大鼠颈动脉窦压力感受器的活动

在36只麻醉大鼠,以隔离灌流颈动脉窦区记录窦神经传入放电的方法观察了腺苷（adenosine,Ado）对颈动脉窦压力感受器传入放电的影响。所得结果如下：（1）以75μmol／LAdo隔离灌流大鼠左侧颈动脉窦区时,窦内压-窦神经传入放电积分（ISP－ISNA）关系曲线向左上方移位,曲线最大斜率（PS）由（18．75±0．12）％／kPa增至（22．21±0．11）％／kPa（P＜0．001）,最大积分值（PIV）由（209．83±2．57）％增至（239．17±1．75）％;阈压（TP）和饱和压（SP）则分别从（8．57±0．24）和（22．99±0．34）下降至（7．15±0．23）kPa（P＜0．001）和（21．21±0,43）kPa（P＜0．01）。再分别以125和175μmol／LAdo灌流,机能曲线进一步向左上方移位,PS、TP和SP的变化均呈明显的剂量依赖性。（2）用腺苷选择性A1受体拮抗剂8－cyclopentyl－1,3－dipropylxanthine（0．134mmol／L）预处理后,Ado的上述效应即被阻断。（3）先给予KATP通道阻断剂格列苯脲（10μmol／L）亦可取消腔苷对窦神经传入放电的影响。结果表明,在体隔离灌流大鼠颈动脉窦区条件下,Ado对颈动脉窦压力感受器活动有易化作用,此作用似与腺苷A1受体介导的KATP通道开放有关。     

Action of substance P and one of its synthetic antagonists on the nucleus tractus solitarius

The study aims to establish the nature of the chemical mediator which produces the IP (presynaptic inhibition) of the mechanoreceptive afferents reaching the NTS (nucleus tractus solitarius) of the frog. To this end we have examined the effects of the administration of SP (substance P) and of one of its antagonists in the IV ventricle, in both normal and unilaterally axotomized preparations at the level of the glossopharyngeal nerve. In particular we have examined the size of the afferent discharge of the glossopharyngeal-hypoglossus reflex arc and the PAD (primary afferent depolarization) phenomena recorded from the dorsal root of the XII. While in normal preparations the SP reduces the size of the reflex discharge, on the contrary the antagonist increases it; the electrical activity of PAD appears to be enhanced by SP and reduced by the antagonist. Lastly SP normalises the enhanced response produced by axotomy. All the observed effects favour the hypothesis that the IP, which appears in the NTS with the activation of the mechanoreceptive afferents, is brought about by the release of S.P. from their central endings.     

A Biofeedback System of Baroreceptor Cardiac Reflex Sensitivity

The evidence presently available suggests that the parasympathetic nervous system and sympathetic-parasympathetic interactions could play a role in the pathophysiology of cardiovascular disorders and, specifically, in hypertension. A loss of sensitivity of the baroreceptor reflex is one of the fundamental mechanisms underlying the deficits found in parasympathetic cardiac control. The baroreceptor reflex is a basic mechanism for the regulation of blood pressure, a powerful source of vagal afferent input to the central nervous system, and one of the most important physiological mechanisms affecting efferent cardiac vagal activity. This paper describes a computerized system for the on-line analysis of the baroreceptor cardiac reflex function using the noninvasive spontaneous sequence method in the time domain. The system provides feedback of the baroreceptor reflex sensitivity (the change in heart period per unit change in systolic blood pressure) differentially both when the systolic blood pressure is increasing and when it is decreasing. The accuracy of the described system has been tested against the conventional off-line procedure. None of the parameters supplied by the analysis show a significant difference between the on-line and off-line methods. These results confirm the accuracy of the on-line system to analyze baroreceptor cardiac reflex function.     

Electrophysiological and neuroanatomical evidence of sexual dimorphism in aortic baroreceptor and vagal afferents in rat

Evidence for sexual dimorphism in autonomic control of cardiovascular function is both compelling and confounding. Across healthy and disease populations sex-associated differences in neurocirculatory hemodynamics are far too complex to be entirely related to sex hormones. As an initial step toward identifying additional physiological mechanisms, we investigated whether there is a sex bias in the relative expression of low-threshold-myelinated and high-threshold-unmyelinated aortic baroreceptor afferents in rats. These two types of afferent fibers have markedly different reflexogenic effects upon heart rate and blood pressure and thus the potential impact upon baroreflex dynamics could be substantial. Our results, using a combination of a patch-clamp study of fluorescently identified aortic baroreceptor neurons (ABN) and morphometric analysis of aortic baroreceptor nerve fibers, demonstrate that females exhibit a greater percentage of myelinated baroreceptor fibers (24.8% vs. 18.7% of total baroreceptor fiber population, P < 0.01) and express a functional subtype of myelinated ABN rarely found in age-matched males (11% vs. 2.3%, n = 107, P < 0.01). Interestingly, this neuronal phenotype is more prevalent in the general population of female vagal afferent neurons (17.7% vs. 3.8%, n = 169, P < 0.01), and ovariectomy does not alter its expression but does lessen neuronal excitability. These data suggest there are fundamental neuroanatomical and electrophysiological differences between aortic baroreceptor afferents of female and male rats. Possible explanations are presented as to how such a greater prevalence of low-threshold myelinated afferents could be a contributing factor to the altered baroreflex sensitivity and vagal tone of females compared with males.     

Analysis of afferent,central, and efferent components of the baroreceptor reflex in mice

Studies of genetically modified mice provide a powerful approach to investigate consequences of altered gene expression in physiological and pathological states. The goal of the present study was to characterize afferent, central, and efferent components of the baroreceptor reflex in anesthetized Webster 4 mice. Baroreflex and baroreceptor afferent functions were characterized by measuring changes in renal sympathetic nerve activity (RSNA) and aortic depressor nerve activity (ADNA) in response to nitroprusside- and phenylephrine-induced changes in arterial pressure. The data were fit to a sigmoidal logistic function curve. Baroreflex diastolic pressure threshold (P(th)), the pressure at 50% inhibition of RSNA (P(mid)), and baroreflex gain (maximum slope) averaged 74 +/- 5 mmHg, 101 +/- 3 mmHg, and 2.30 +/- 0.54%/mmHg, respectively (n = 6). The P(th), P(mid), and gain for the diastolic pressure-ADNA relation (baroreceptor afferents) were similar to that observed for the overall reflex averaging 79 +/- 9 mmHg, 101 +/- 4 mmHg, and 2.92 +/- 0.53%/mmHg, respectively (n = 5). The central nervous system mediation of the baroreflex and the chronotropic responsiveness of the heart to vagal efferent activity were independently assessed by recording responses to electrical stimulation of the left ADN and the peripheral end of the right vagus nerve, respectively. Both ADN and vagal efferent stimulation induced frequency-dependent decreases in heart rate and arterial pressure. The heart rate response to ADN stimulation was nearly abolished in mice anesthetized with pentobarbital sodium (n = 4) compared with mice anesthetized with ketamine-acepromazine (n = 4), whereas the response to vagal efferent stimulation was equivalent under both types of anesthesia. Application of these techniques to studies of genetically manipulated mice can be used to identify molecular mechanisms of baroreflex function and to localize altered function to afferent, central, or efferent sites.     

Theoretical and electrophysiological evidence for axial loading about aortic baroreceptor nerve terminals in rats

Arterial baroreceptors are essential for neurocirculatory control, providing rapid hemodynamic feedback to the central nervous system. The pressure-dependent discharge of carotid and aortic baroreceptor afferents has been extensively studied. A common assumption has been that circumferential deformation of the arterial wall is the predominant mechanical force affecting baroreceptor discharge. However, in vivo the arterial tree is under significant longitudinal tension, leading to the hypothesis that axially directed forces may contribute to baroreceptor function. To test this hypothesis, we utilized a combination of finite element modeling methods and an in vitro rat aortic arch preparation. Model formulation utilized traditional analytic constructs available in the literature followed by refinement of model material parameters through direct comparison of computationally and experimentally generated pressure-diameter curves. The numerical simulations strongly indicated a functional role for axial loading within the region of the baroreceptive nerve terminal. This prediction was confirmed through single-fiber recording of baroreceptor nerve discharge under conditions with and without longitudinal tension in the vessel preparation. The recordings (n = 5) demonstrated that longitudinal tension significantly (P < 0.02) lowered both the pressure threshold (P(th), mmHg) for baroreceptor discharge and sensitivity (S(th), Hz/mmHg). The effect was nearly instantaneous and sustained; i.e., under longitudinal tension average P(th) was 84 +/- 3 mmHg and S(th) was 0.71 +/- 0.15 Hz/mmHg, which immediately increased to a P(th) of 94 +/- 4 mmHg and a S(th) of 1.20 +/- 0.32 Hz/mmHg with loss of axial tension. Possible explanations of how an abrupt change in axial loading could result in a synchronized increase in afferent drive of the baroreceptor reflex, and the potentiating effect this could have on neurogenically mediated orthostatic intolerance are discussed.     

卧床前后压力感受性反射机能变化的研究

许多数据表明长期失重以后立位耐力降低可能与压力感受性反射功能的改变有关。本文比较了两组被试者15天低动力卧床前后的立位耐力。以血压调节模型为基础分析了两种不同方式卧床前后单纯立位和下身负压加立位时压力感受性反射功能的改变,并用颈部加压及下身负压对中枢调节功能改变进行了观察。结果表明严格的头低位卧床后,立位耐力下降及压力感受性反射功能改变明显大于半日平卧半日倚坐者。而压力感受性反射功能的改变,特别是中枢神经系统调节功能的紊乱,是卧床后立位耐力降低的主要原因。从这种考虑为基础,作者提出了改变失重或模拟失重状态下的血液分布,调整对压力感受器的刺激,可能是预防心血管失调的有效方法。     

Baroreceptor afferent discharge in the pregnant rat

Pregnancy is associated with blunted reflex responses to cardiac and arterial baroreceptor stimulation. We tested the hypothesis that arterial baroreceptor afferent discharge is attenuated in response to a pressure stimulus in pregnant rats. Multifiber aortic depressor nerve activity (ADNA), mean arterial pressure (MAP), and heart rate were measured in anesthetized (pentobarbital sodium, 35 mg/kg ip) late-pregnant and virgin rats in response to increases ?phenylephrine (PE), 1.5-24 microg. kg(-1). min(-1) and 1-16 microg/kg and decreases ?sodium nitroprusside (SNP), 5-80 microg. kg(-1). min(-1) and 0.05-16 microg/kg in MAP. Resting MAP was lower in pregnant rats, but changes in MAP were similar to those in virgin rats during both PE and SNP administration. ADNA was significantly attenuated in pregnant animals during both PE and SNP infusions (P < 0.05) due to a more rapid adaptation to the pressure stimulus. Bolus drug administration evoked similar changes in MAP and ADNA in both groups; however, the maximum decrease in ADNA was achieved at the lowest dose of SNP in pregnant rats. Thus baroreceptor afferent discharge is attenuated in pregnant rats, and this involves a more rapid adaptation to a pressure stimulus.     

Detection of cold pain, cold allodynia and cold hyperalgesia in freely behaving rats

In mammals, somatosensory input activates feedback and feed-forward inhibitory circuits within the spinal cord dorsal horn to modulate sensory processing and thereby affecting sensory perception by the brain. Conventionally, feedback and feed-forward inhibitory activity evoked by somatosensory input to the dorsal horn is believed to be driven by glutamate, the principle excitatory neurotransmitter in primary afferent fibers. Substance P (SP), the prototypic neuropeptide released from primary afferent fibers to the dorsal horn, is regarded as a pain substance in the mammalian somatosensory system due to its action on nociceptive projection neurons. Here we report that endogenous SP drives a novel form of feed-forward inhibitory activity in the dorsal horn. The SP-driven feed-forward inhibitory activity is long-lasting and has a temporal phase distinct from glutamate-driven feed-forward inhibitory activity. Compromising SP-driven feed-forward inhibitory activity results in behavioral sensitization. Our findings reveal a fundamental role of SP in recruiting inhibitory activity for sensory processing, which may have important therapeutic implications in treating pathological pain conditions using SP receptors as targets.     

Plasticity in the nucleus tractus solitarius and its influence on lung and airway reflexes.

The nucleus tractus solitarius (NTS) is the first central nervous system (CNS) site for synaptic contact of the primary afferent fibers from the lungs and airways. The signal processing at these synapses will determine the output of the sensory information from the lungs and airways to all downstream synapses in the reflex pathways. The second-order NTS neurons bring to bear their own intrinsic and synaptic properties to temporally and spatially integrate the sensory information with inputs from local networks, higher brain regions, and circulating mediators, to orchestrate a coherent reflex output. There is growing evidence that NTS neurons share the rich repertoire of forms of plasticity demonstrated throughout the CNS. This review focuses on existing evidence for plasticity in the NTS, potential targets for plasticity in the NTS, and the impact of this plasticity on lung and airway reflexes.