Electrophysiological Properties of Rostral Ventrolateral Medulla Neurons in Angiotensin II 1a Receptor Knockout Mice

Matsuura, Tomokazu; Kumagai, Hiroo; Onimaru, Hiroshi; Kawai, Akira; Iigaya, Kamon; Onami, Toshiko; Sakata, Katsufumi; Oshima, Naoki; Sugaya, Takeshi; Saruta, Takao

doi:10.1161/01.hyp.0000173421.97463.ac

Cited by 33 publications

(41 citation statements)

References 37 publications

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“…[12][13][14][15][16][17][18][19][20] The experimental protocols were approved by the Institutional Review Board of National Defense Medical College and were in accordance with the National Guidelines for the Conduct of Animal Experiments. Briefly, the animals received deep ether anesthesia, and the brainstem-spinal cord was isolated at the Th 2 level (Figure 1a).…”

Section: General Preparationsmentioning

confidence: 99%

“…To avoid recording respiratory neuronal activity, we examined phrenic nerve activity from the ventral root of C 4 ( Figure 1a) and excluded neurons with a strong phase relationship with the phrenic nerve discharge from further study. 12,16,17 Patch-clamp electrodes Electrodes were pulled in one stage from thin-wall borosilicate filament capillaries (GC100TF-10, outer diameter 1.0 mm, Clark Electromed, Reading, UK) using a vertical puller. The electrodes had a tip diameter of 1.8-2.0 mm and a resistance of 4-6 MO.…”

Section: General Preparationsmentioning

confidence: 99%

“…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%

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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: General Preparationsmentioning

confidence: 99%

Section: General Preparationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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%

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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Cardiovascular effects of angiotensin II in the rostral ventrolateral medulla: The push-pull hypothesis

Dampney

Tan²,

Sheriff³

et al. 2007

Current Science Inc

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Neurons within the rostral ventrolateral medulla (RVLM) play a pivotal role in the tonic and phasic control of blood pressure. This region also contains a high density of angiotensin II type 1 (AT1) receptors. There is evidence that tonic activation of AT1 receptors in the RVLM contributes to an increased sympathetic vasomotor activity in some models of hypertension. At the same time, under certain conditions, activation of AT1 receptors in the RVLM can cause sympathoinhibition. In this review we argue that the effect of endogenous angiotensin II in the RVLM on sympathetic vasomotor activity depends upon the balance between tonic excitatory and inhibitory effects on sympathetic premotor neurons mediated by AT1 receptors within this region, and that this balance may be altered in different physiological or pathophysiological conditions.

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Electrophysiological Properties of Rostral Ventrolateral Medulla Neurons in Angiotensin II 1a Receptor Knockout Mice

Cited by 33 publications

References 37 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

Cardiovascular effects of angiotensin II in the rostral ventrolateral medulla: The push-pull hypothesis

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