Importance of rostral ventrolateral medulla neurons in determining efferent sympathetic nerve activity and blood pressure

Accentuated sympathetic nerve activity (SNA) is a risk factor for cardiovascular events. In this review, we investigate our working hypothesis that potentiated activity of neurons in the rostral ventrolateral medulla (RVLM) is the primary cause of experimental and essential hypertension. Over the past decade, we have examined how RVLM neurons regulate peripheral SNA, how the sympathetic and renin-angiotensin systems are correlated and how the sympathetic system can be suppressed to prevent cardiovascular events in patients. Based on results of whole-cell patch-clamp studies, we report that angiotensin II (Ang II) potentiated the activity of RVLM neurons, a sympathetic nervous center, whereas Ang II receptor blocker (ARB) reduced RVLM activities. Our optical imaging demonstrated that a longitudinal rostrocaudal column, including the RVLM and the caudal end of ventrolateral medulla, acts as a sympathetic center. By organizing and analyzing these data, we hope to develop therapies for reducing SNA in our patients. Recently, 2-year depressor effects were obtained by a single procedure of renal nerve ablation in patients with essential hypertension. The ablation injured not only the efferent renal sympathetic nerves but also the afferent renal nerves and led to reduced activities of the hypothalamus, RVLM neurons and efferent systemic sympathetic nerves. These clinical results stress the importance of the RVLM neurons in blood pressure regulation. We expect renal nerve ablation to be an effective treatment for congestive heart failure and chronic kidney disease, such as diabetic nephropathy

Effects of Feeding-Related Peptides on Neuronal Oscillation in the Ventromedial Hypothalamus

The ventromedial hypothalamus (VMH) plays an important role in feeding behavior, obesity, and thermoregulation. The VMH contains glucose-sensing neurons, the firing of which depends on the level of extracellular glucose and which are involved in maintaining the blood glucose level via the sympathetic nervous system. The VMH also expresses various receptors of the peptides related to feeding. However, it is not well-understood whether the action of feeding-related peptides mediates the activity of glucose-sensing neurons in the VMH. In the present study, we examined the effects of feeding-related peptides on the burst-generating property of the VMH. Superfusion with insulin, pituitary adenylate cyclase-activating polypeptide, corticotropin-releasing factor, and orexin increased the frequency of the VMH oscillation. In contrast, superfusion with leptin, cholecystokinin, cocaine- and amphetamine-regulated transcript, galanin, ghrelin, and neuropeptide Y decreased the frequency of the oscillation. Our findings indicated that the frequency changes of VMH oscillation in response to the application of feeding-related peptides showed a tendency similar to changes of sympathetic nerve activity in response to the application of these substances to the brain

Platypnea-orthodeoxia syndrome in the right lateral decubitus position: a case report

Abstract Background Platypnea-orthodeoxia syndrome is a rare syndrome characterized by dyspnea and hypoxia when the patient is sitting or standing. Here we report a case of platypnea-orthodeoxia syndrome caused by a right hemidiaphragmatic elevation with giant liver cyst that triggered a right-to-left shunt through the patent foramen ovale. This case report is the first presentation of a case secondary to hemidiaphragmatic elevation with giant liver cyst. In addition to this, a malposition of the pacemaker lead could be associated with platypnea-orthodeoxia syndrome in this case. Case presentation A 91-year-old Japanese woman presented to our hospital with hypoxia of unknown origin. Severe hypoxia and cyanosis were observed only in the right lateral decubitus position. A chest X-ray and computed tomography scan revealed right hemidiaphragmatic elevation, which was probably compressing the right atrium. A transesophageal echocardiogram showed a compressed right atrium and shunt blood flow in both directions: from the left to the right atrium and vice versa. The shunt flow was exacerbated by postural changes from the left to the right lateral decubitus. A transesophageal echocardiogram also confirmed compression of the right atrium due to giant liver cyst and a malposition of the pacemaker lead abnormally placed in the left atrium through patent foramen ovale. We concluded that the cause of hypoxia was platypnea-orthodeoxia syndrome with right-to-left interatrial shunt through patent foramen ovale. Surgical closure of patent foramen ovale was not performed due to the age of our patient, surgical difficulties, and failure to obtain informed consent. For these reasons she was discharged after receiving medical advice about her posture. Conclusions Platypnea-orthodeoxia syndrome is rare and difficult to diagnose. The present case suggests that hypoxia due to postural changes should be considered a differential diagnosis of platypnea-orthodeoxia syndrome

Monosynaptic excitatory connection from the rostral ventrolateral medulla to sympathetic preganglionic neurons revealed by simultaneous recordings

To directly investigate whether a monosynaptic connection exists between neurons in the rostral ventrolateral medulla (RVLM) and sympathetic preganglionic neurons (SPNs), we used simultaneous extracellular recordings of RVLM neurons and whole-cell patch-clamp recordings of SPNs at the Th2 level and analyzed them by spike-triggered averaging. We averaged 200 sweeps of membrane potentials in SPN triggered by the spikes in the RVLM neuron. No clear postsynaptic potentials were detected in the averaged wave of SPNs before angiotensin II (Ang II) superfusion, whereas during superfusion with Ang II (6 micromol/L) on the medulla oblongata side alone excitatory postsynaptic potentials (EPSPs) were clearly found in the SPN of 3 out of 10 pairs at 40 +/- 1 ms after the averaged triggering spike in the RVLM neuron. We consider them to be monosynaptic EPSPs, because 1) the averaged EPSPs exhibited a sharp rise time, 2) the onset latency of the averaged EPSPs in the SPNs after the trigger spike in the RVLM was the same as the latency of the antidromic action potentials in the RVLM neurons in response to electrical stimulation of the SPNs, and 3) the amplitude of the averaged EPSPs was over 2 mV. In summary, combining simultaneous recording and spike-triggered averaging allowed us to demonstrate a monosynaptic excitatory connection between a single RVLM neuron and a single SPN in the thoracic spinal cord. Such connections provide the basis for the maintenance of sympathetic tone and the integrative reflex that relays through the RVLM. The results explain the mechanism by which Ang II in the RVLM area increases peripheral sympathetic activity and blood pressure.10 page(s