Novel axonal projection from the caudal end of the ventrolateral medulla to the intermediolateral cell column

Iigaya, Kamon; Kumagai, Hiroo; Onimaru, Hiroshi; Kawai, Akira; Oshima, Naoki; Onami, Toshiko; Takimoto, Chie; Kamayachi, Tadashi; Hayashi, Kôichi; Saruta, Takao; Itoh, Hiroshi

doi:10.1152/ajpregu.00254.2006

Cited by 12 publications

(18 citation statements)

References 31 publications

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“…Thus, in the present study, we investigated the effect of aldosterone, eplerenone (an MR blocker), FAD286 (an aldosterone synthase inhibitor) and benzamil (an epithelial sodium channel (ENaC) blocker) on bulbospinal RVLM neurons using brainstem-spinal cord preparations that preserved the sympathetic nervous system. [11][12][13][14][15][16][17][18][19][20] As a previous report showed that intracerebroventricular infusion of eplerenone lowered blood pressure, 2, 21 we examined the direct effect of eplerenone on RVLM neurons, using a low-Ca 2 þ , high-Mg 2 þ solution to block synaptic input into RVLM neurons. Aldosterone performs its function in the collecting ducts of the kidneys, and ENaCs are known to participate in the process through genomic action.…”

Section: Introductionmentioning

confidence: 99%

Aldosterone is synthesized in and activates bulbospinal neurons through mineralocorticoid receptors and ENaCs in the RVLM

et al. 2013

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The effects of aldosterone and mineralocorticoid receptor (MR) blockers on presympathetic neurons in the rostral ventrolateral medulla (RVLM) are well studied. To directly investigate whether aldosterone, eplerenone (an MR blocker), FAD286 (an aldosterone synthase inhibitor) and benzamil (an epithelial sodium channel (ENaC) blocker) affect RVLM neurons, we examined changes in the membrane potentials (MPs) of bulbospinal RVLM neurons using the whole-cell patch-clamp technique during superfusion with these drugs to brainstem-spinal cord preparations. Aldosterone superfusion (0.1 lmol/l) depolarized the RVLM neurons. In contrast, eplerenone superfusion (1 lmol/l) hyperpolarized them. To evaluate the existence of aldosterone, FAD286 superfusion (10 lmol/l) was performed, and the RVLM neurons became hyperpolarized during FAD superfusion. These data suggest that MRs exist and that aldosterone is synthesized in the brainstem. Benzamil superfusion (1 lmol/l) hyperpolarized the RVLM neurons. To clarify whether aldosterone, eplerenone, FAD286 and benzamil acted directly on the RVLM neurons, a lowCa 2 þ , high-Mg 2 þ solution was used to block the synaptic input to the RVLM neurons, and the above-mentioned drugs were added during the low-Ca 2 þ superfusion. During the aldosterone superfusion, the RVLM neurons became depolarized, and they became hyperpolarized during eplerenone, FAD286 or benzamil superfusion. Importantly, when aldosterone was superfused after the benzamil solution, the MPs of the RVLM neurons did not depolarize. These results suggest that MRs are present in the RVLM neurons and that aldosterone is synthesized in the RVLM. The RVLM neurons themselves possess ENaCs, and ENaCs are the underlying mechanism by which aldosterone activates RVLM neurons. Hypertension Research (2013) 36, 504-512; doi:10.1038/hr.2012.224; published online 31 January 2013Keywords: aldosterone; benzamil; FAD286; RVLM neurons; whole-cell patch clamp INTRODUCTIONThe actions of aldosterone include vasoconstriction, vascular fibrosis, endothelial dysfunction, and sodium reabsorption and retention. These actions contribute to hypertension. However, recently, many studies have demonstrated the relationship between aldosterone and sympathetic nerve activity. In fact, aldosterone has been shown to cross the blood-brain barrier relatively easily, 1 as clarified using the model developed by Gomez-Sanchez et al. 2 showed that the intracerebroventricular infusion of antagonists of the mineralocorticoid receptor (MR), at a dose that had no effect systemically, lowered blood pressure. Intracerebroventricular infusion of aldosterone increased blood pressure, 3 and MRs were found in the brain. 4 Furthermore, aldosterone is involved in remodeling after myocardial infarction, and central blockade of aldosterone has been shown to attenuate cardiac remodeling. 5,6 Recent studies have demonstrated the existence of an aldosterone system in the brain, 4 and an increase in [Na þ ] in cerebrospinal fluid

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Section: Introductionmentioning

confidence: 99%

Aldosterone is synthesized in and activates bulbospinal neurons through mineralocorticoid receptors and ENaCs in the RVLM

et al. 2013

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“…[7][8][9][10][11][12][13][14]17,18 The protocols of the experiments were approved by the Institutional Review Board of Keio University School of Medicine, Tokyo, and were in accord with the National Guidelines for the Conduct of Animal Experiments. With the animals under deep ether anesthesia, the brainstem-spinal cord was isolated together with other organs (including the heart, carotid sinuses and aorta), which were maintained intact ( Figure 1).…”

Section: General Preparationsmentioning

confidence: 99%

“…[7][8][9][10][11][12][13][14] In an earlier study, 9 we performed whole-cell recordings of rostral ventrolateral medulla (RVLM) neurons and classified them into three types according to their discharge patterns. We have also demonstrated monosynaptic connections between neurons in the RVLM and sympathetic pre-ganglionic neurons by simultaneous recording using the same preparation.…”

Section: Introductionmentioning

confidence: 99%

“…13 Furthermore, we identified a monosynaptic (axonal) projection extending from the caudal end of the ventrolateral medulla to the inter-mediolateral cell column using optical imaging and recorded the electrical transmission using a motion picture. 12 In the present study, we developed a modified brainstem-spinal cord preparation in which the aortic arch, carotid sinuses and baroreceptor afferent nerves remained intact. This new preparation enabled us to record the membrane potentials of baro-sensitive neurons in the brainstem and spinal cord region.…”

Section: Introductionmentioning

confidence: 99%

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Baro-excited neurons in the caudal ventrolateral medulla (CVLM) recorded using the whole-cell patch-clamp technique

et al. 2011

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Caudal ventrolateral medulla (CVLM) neurons have important roles in the regulation of sympathetic nerve activity and blood pressure through their tonic inhibition of rostral ventrolateral medulla neurons. As few reports have demonstrated CVLM neuronal activity using the whole-cell patch-clamp technique, we attempted to find neurons in the CVLM that are depolarized by the stimulation of baroreceptors. To record the membrane potentials of the neurons in the CVLM, we developed a modified brainstem-spinal cord preparation that enabled us to change the pressure exerted on the aortic arch and carotid sinuses. We were able to identify neurons in the CVLM in which they were depolarized and the action potential (AP) frequency was increased upon baroreceptor stimulation. We referred to these neurons as baro-excited CVLM neurons. When these preparations were superfused with an angiotensin-II (Ang-II) solution, the frequency of the APs increased in 10 of the 14 baro-excited CVLM neurons. Superfusion with a low-Ca 2+ , high-Mg 2+ solution abolished the APs in all seven baro-excited CVLM neurons, suggesting that the baro-excited CVLM neurons did not fire spontaneously. When the preparation was superfused with a low-Ca 2+ solution, 6 of the 7 baro-excited CVLM neurons did not respond to Ang-II superfusion. We for the first time found the baro-excited CVLM neurons, which depolarized pressure dependently but may not fire spontaneously. As Ang-II did not change the activity of the CVLM neurons during superfusion with a low-Ca 2+ , high-Mg 2+ solution, the presynaptic neurons may be mandatory for the Ang-II-induced activation of postsynaptic baro-excited CVLM neurons.

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“…[14][15][16][17][18][19][20][21][22] While recording the membrane potentials (MPs) of the bulbospinal RVLM neurons using the patch-clamp technique, the neurons were superfused with metoprolol (b 1 -AR antagonist), dobutamine (b 1 -AR agonist), butoxamine (b 2 -AR antagonist) or salbutamol (b 2 -AR agonist). Furthermore, to examine the direct effects of metoprolol or butoxamine on the RVLM neurons, the superfusion was conducted with each drug dissolved in a low-Ca 2 þ , high-Mg 2 þ or tetrodotoxin (TTX) solution.…”

Section: Introductionmentioning

confidence: 99%

Expression and functions of β1- and β2-adrenergic receptors on the bulbospinal neurons in the rostral ventrolateral medulla

et al. 2014

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The expression and effects of b-adrenergic receptors (b-ARs) on the neurons of the bulbospinal rostral ventrolateral medulla (RVLM) have been limitedly examined to date. The objective of this study was to examine the expression of b 1 -and b 2 -ARs on the bulbospinal RVLM neurons electrophysiologically and histologically. To directly investigate whether RVLM neurons display sensitivity to metoprolol (a b 1 -AR antagonist), dobutamine (a b 1 -AR agonist), butoxamine (a b 2 -AR antagonist), and salbutamol (a b 2 -AR agonist), we examined changes in the membrane potentials of the bulbospinal RVLM neurons using the whole-cell patch-clamp technique during superfusion of these drugs. During metoprolol superfusion, 16 of the 20 RVLM neurons were hyperpolarized, and 5 of the 6 RVLM neurons were depolarized during dobutamine superfusion. During butoxamine superfusion, 11 of the 16 RVLM neurons were depolarized, and all of the 8 RVLM neurons were hyperpolarized during salbutamol superfusion. These results suggest the expression of b 1 -and b 2 -ARs on the RVLM neurons. To determine the presence of b 1 -and b 2 -ARs histologically, immunofluorescence examination was performed. Five metoprolol-hyperpolarized neurons were examined for b 1 -AR and tyrosine hydroxylase (TH) immunoreactivity. All of the neurons displayed b 1 -AR immunoreactivity, whereas three of the neurons displayed TH immunoreactivity. All of the five RVLM neurons that became depolarized during metoprolol superfusion and hyperpolarized during butoxamine superfusion displayed b 1 -and b 2 -AR immunoreactivity. Our findings suggest that b 1 -AR antagonists or b 2 -AR agonists may decrease blood pressure through decreasing the activity of the bulbospinal RVLM neurons.

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Novel axonal projection from the caudal end of the ventrolateral medulla to the intermediolateral cell column

Cited by 12 publications

References 31 publications

Aldosterone is synthesized in and activates bulbospinal neurons through mineralocorticoid receptors and ENaCs in the RVLM

Aldosterone is synthesized in and activates bulbospinal neurons through mineralocorticoid receptors and ENaCs in the RVLM

Baro-excited neurons in the caudal ventrolateral medulla (CVLM) recorded using the whole-cell patch-clamp technique

Expression and functions of β1- and β2-adrenergic receptors on the bulbospinal neurons in the rostral ventrolateral medulla

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