Projection neurons of the vestibulo‐sympathetic reflex pathway

Changes in head position and posture are detected by the vestibular system and are normally followed by rapid modifications in blood pressure. These compensatory adjustments, which allow humans to stand up without fainting, are mediated by integration of vestibular system pathways with blood pressure control centers in the ventrolateral medulla. Orthostatic hypotension can reflect altered activity of this neural circuitry. Vestibular sensory input to the vestibulo‐sympathetic pathway terminates on cells in the vestibular nuclear complex, which in turn project to brainstem sites involved in the regulation of cardiovascular activity, including the rostral and caudal ventrolateral medullary regions (RVLM and CVLM, respectively). In the present study, sinusoidal galvanic vestibular stimulation was used to activate this pathway, and activated neurons were identified through detection of c‐Fos protein. The retrograde tracer Fluoro‐Gold was injected into the RVLM or CVLM of these animals, and immunofluorescence studies of vestibular neurons were conducted to visualize c‐Fos protein and Fluoro‐Gold concomitantly. We observed activated projection neurons of the vestibulo‐sympathetic reflex pathway in the caudal half of the spinal, medial, and parvocellular medial vestibular nuclei. Approximately two‐thirds of the cells were ipsilateral to Fluoro‐Gold injection sites in both the RVLM and CVLM, and the remainder were contralateral. As a group, cells projecting to the RVLM were located slightly rostral to those with terminals in the CVLM. Individual activated projection neurons were multipolar, globular, or fusiform in shape. This study provides the first direct demonstration of the central vestibular neurons that mediate the vestibulo‐sympathetic reflex. J. Comp. Neurol. 522:2053–2074, 2014. © 2013 Wiley Periodicals, Inc.     

Cardiovascular Responses to Somatosensory Stimulation and Their Modulation by Baroreflex Mechanisms

Exposure of experimental animals to noxious somatic stimulations sometimes induces sustained hypertension. Information regarding the medullary projections of somatic afferents and the neurotransmitters involved in them is incomplete. The present investigation in urethane-anesthetized, artificially ventilated, adult male Wistar rats was undertaken to clarify some of these issues. It was observed that the inhibition of contralateral, ipsilateral, or bilateral rostral ventrolateral medullary pressor area (RVLM) with muscimol attenuated the pressor and tachycardic responses to sciatic nerve stimulation. Similar inhibition of the medial subnucleus of the solitary tract (mNTS) exaggerated the cardiovascular responses to sciatic nerve stimulation. Interruption of the baroreflex by microinjections of ionotropic glutamate receptor antagonists into the mNTS or barodenervation also exaggerated the responses to sciatic nerve stimulation. Unilateral stimulation of the aortic nerve blocked the cardiovascular responses to the sciatic nerve stimulation. These results indicated that in the rat, the ascending afferents in the sciatic nerve project bilaterally to the RVLM as well as mNTS; an excitatory amino acid, probably glutamate, is released in the mNTS in response to the sciatic nerve stimulation; and barodenervation or blockade of baroreflex in the mNTS exaggerates, while baroreceptor stimulation inhibits, cardiovascular responses to somatosensory stimulation.     

The role of the brain renin–angiotensin system in hypertension: Implications for new treatment

Hypertension affects 26% of adults and is in constant progress related to increased incidence of obesity and diabetes. One-third of hypertensive patients may be successfully treated with one antihypertensive agent, one-third may require two agents and in the remaining patients will need three agents for effective blood pressure (BP) control. The development of new classes of antihypertensive agents with different mechanisms of action therefore remains an important goal. Brain renin–angiotensin system (RAS) hyperactivity has been implicated in hypertension development and maintenance in several types of experimental and genetic hypertension animal models. Among the main bioactive peptides of the brain RAS, angiotensin (Ang) II and Ang III have similar affinities for type 1 (AT1) and type 2 (AT2) Ang II receptors. Following intracerebroventricular (i.c.v.) injection, Ang II and Ang III similarly increase arginine–vasopressin (AVP) release and BP. Blocking the brain RAS may be advantageous as it simultaneously (1) decreases sympathetic tone and consequently vascular resistance, (2) decreases AVP release, reducing blood volume and vascular resistance and (3) blocks angiotensin-induced baroreflex inhibition, decreasing both vascular resistance and cardiac output. However, as Ang II is converted to Ang III in vivo, the exact nature of the active peptide is not precisely determined. We summarize here the main findings identifying AngIII as one of the major effector peptides of the brain RAS in the control of AVP release and BP. Brain AngIII exerts a tonic stimulatory effect on BP in hypertensive rats, identifying brain aminopeptidase A (APA), the enzyme generating brain Ang III, as a potentially candidate target for hypertension treatment. This has led to the development of potent orally active APA inhibitors, such as RB150 — the prototype of a new class of centrally acting antihypertensive agents.     

延髓血压相关单位电活动与去甲肾上腺素抗低血压的关系

在32只家兔的延髓头端腹外侧区(rVLM)记录到具有自发放电活动的血压相关单位57个。在以去甲肾上腺素(NE)抗硝普钠所致的低血压过程中,49个单位(85.9％)放电受到抑制(抑制反应单位),8个单位(14.1％)放电增加(兴奋反应单位)。所有血压相关单位散在分布于外侧网状核(N.RL)、巨细胞网状核(N.Rgc)腹外侧及小细胞网状核(N.Rpc)腹侧。结果提示去甲肾上腺素抗低血压时,延髓血压相关神经元以抑制性反应为主。     

Adrenaline contributes to prenatal respiratory maturation in rat medulla-spinal cord preparation

Adrenaline is a potent respiratory regulator. However, adrenergic contribution to the developing respiratory center has not been studied extensively. Adrenaline application on embryonic day 17 medulla-spinal cord block preparations abolished non-respiratory activity and enhanced respiratory frequency. Phentolamine application on neonatal blocks that produced stable neonatal respiration resulted in respiratory destabilization. These results suggest that central adrenergic modulation is involved in fetal respiratory development and maintenance of stable respiration.     

Upper limb kinesthetic asymmetries: Gender and handedness effects

Proprioceptive and motor information contribute to movement representation; however, the equivalence of homologous contralateral sensorimotor processes as a function of gender and handedness has received little attention. The present work investigated asymmetry in contralateral reproductions of movements elicited by tendon vibration in right and left handed young adults of both genders. With eyes closed, illusions of elbow flexion movement elicited by a 100 Hz vibration applied to the distal tendon of the right or left triceps muscle were matched concurrently with the opposite limb. Overall, movement velocity was larger for females than males, asymmetric and handedness dependent in males. Conversely, consistent symmetry was found between left and right-handed females. These findings lead us to suggest that hand preference and gender contribute to differences in movement representation that may result from the combination of cortical structural differences and information processing specific to each hemisphere and gender.     

Expression of the M3 Muscarinic Receptor on Orexin Neurons that Project to the Rostral Ventrolateral Medulla

Activation of central cholinergic receptors causes a pressor response in rats, and the hypothalamus is important for this response. Projections from hypothalamic orexin neurons to the rostral ventrolateral medulla (RVLM) are involved in sympatho‐excitation of the cardiovascular system. A small population of orexin neurons is regulated by cholinergic inputs through M₃ muscarinic acetylcholine receptor (M₃R). To elucidate whether the M₃R on orexin neurons is involved in cardiosympathetic regulation through the RVLM, we examined the presence of the M₃R on retrograde‐labeled RVLM‐projecting orexin neurons. The retrograde tracer was unilaterally injected into the RVLM. Within the hypothalamus, retrograde‐labeled neurons were located predominantly ipsilateral to the injection side. In the anterior hypothalamus (?1.5 to ?2.3 mm to the bregma), retrograde‐labeled neurons were densely distributed in the paraventricular nuclei and scattered in the retrochiasmatic area. At ?2.3 to ?3.5 mm from the bregma, labeled neurons were located in the regions where orexin neurons were situated, that is, the tuberal lateral hypothalamic area, perifornical area, and dorsomedial nuclei. Very few retrograde‐labeled neurons were observed in the hypothalamus at ?3.5 to ?4.5 mm from the bregma. About 19.5% ± 1.6% of RVLM‐projecting neurons in the tuberal hypothalamus were orexinergic. The M₃R was present on 18.7% ± 3.0% of RVLM‐projecting orexin neurons. Injection of a muscarinic agonist, oxotremorine, in the perifornical area resulted in a pressor response, which was attenuated by a pretreatment of atropine. We conclude that cholinergic inputs to orexin neurons may be involved in cardiosympathetic regulation through the M₃R on the orexin neurons that directly project to the RVLM. Anat Rec, 299:660–668, 2016. © 2016 Wiley Periodicals, Inc.     

Hypotensive but not normotensive haemorrhage increases tryptophan hydroxylase-2 mRNA in caudal midline medulla

Severe blood loss triggers shock, a precipitous hypotension and bradycardia. The integrity of (i) neurons in the vasodepressor region of the caudal midline medulla and (ii) central 5-HT neurotransmission are critical for the expression of haemorrhagic shock. This study investigated whether progressive blood loss triggers altered synthesis of 5-HT in the vasodepressor region of the caudal midline medulla by measuring changes in relative expression levels of tryptophan hydroxylase 2 (TpH 2) mRNA, the rate-limiting enzyme in the synthesis of neuronal 5-HT. Hypotensive but not normotensive haemorrhage triggered a significant increase in TpH 2 mRNA in the vasodepressor region of the caudal midline medulla, identifying an important role for 5-HT-containing caudal midline medullary neurons in haemorrhagic shock.