OBJECTIVES: Nerve growth factor (NGF) induces neuron transdifferentiation of adrenal medulla chromaffin cells (AMCCs) and consequently downregulates the secretion of epinephrine (EPI), which may be involved in the pathogenesis of bronchial asthma. Mammalian achaete scute-homologous 1 (MASH1), a key regulator of neurogenesis in the nervous system, has been proved to be elevated in AMCCs with neuron transdifferentiation in vivo. This study aims to explore the role of MASH1 in the process of neuron transdifferentiation of AMCCs and the mechanisms. METHODS: Rat AMCCs were isolated and cultured. AMCCs were transfected with siMASH1 or MASH1 overexpression plasmid, then were stimulated with NGF and/or dexamethasone, PD98059 (a MAPK kinase-1 inhibitor) for 48 hours. Morphological changes were observed using light and electron microscope. Phenylethanolamine-N-methyltransferase (PNMT, the key enzyme for epinephrine synthesis) and tyrosine hydroxylase were detected by immunofluorescence. Western blotting was used to test the protein levels of PNMT, MASH1, peripherin (neuronal markers), extracellular regulated protein kinases (ERK), phosphorylated extracellular regulated protein kinases (pERK), and JMJD3. Real-time RT-PCR was applied to analyze the mRNA levels of MASH1 and JMJD3. EPI levels in the cellular supernatant were measured using ELISA. RESULTS: Cells with both tyrosine hydroxylase and PNMT positive by immunofluorescence were proved to be AMCCs. Exposure to NGF, AMCCs exhibited neurite-like processes concomitant with increases in pERK/ERK, peripherin, and MASH1 levels (all P<0.05). Additionally, impairment of endocrine phenotype was proved by a signifcant decrease in the PNMT level and the secretion of EPI from AMCCs (all P<0.01). MASH1 interference reversed the effect of NGF, causing increases in the levels of PNMT and EPI, conversely reduced the peripherin level and cell processes (all P<0.01). MASH1 overexpression significantly increased the number of cell processes and peripherin level, while decreased the levels of PNMT and EPI (all P<0.01). Compared with the NGF group, the levels of MASH1, JMJD3 protein and mRNA in AMCCs in the NGF+PD98059 group were decreased (all P<0.05). After treatment with PD98059 and dexamethasone, the effect of NGF on promoting the transdifferentiation of AMCCs was inhibited, and the number of cell processes and EPI levels were decreased (both P<0.05). In addition, the activity of the pERK/MASH1 pathway activated by NGF was also inhibited. CONCLUSIONS MASH1 is the key factor in neuron transdifferentiation of AMCCs. NGF-induced neuron transdifferentiation is probably mediated via pERK/MASH1 signaling.
Animals ; Rats ; Adrenal Medulla ; Cell Transdifferentiation ; Chromaffin Cells ; Dexamethasone ; Epinephrine/pharmacology* ; Mammals ; Nerve Growth Factor ; Neurons ; Peripherins ; Protein Kinases ; Tyrosine 3-Monooxygenase

Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl⁻ absorption and HCO₃⁻ secretion largely through pendrin-dependent Cl⁻/HCO₃⁻ exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO₃ administration. In some rodent models, pendrin-mediated HCO₃⁻ secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl⁻ absorption, but also by modulating the aldosterone response for epithelial Na⁺ channel (ENaC)-mediated Na⁺ absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure.
Absorption ; Acid-Base Equilibrium ; Adrenal Medulla ; Aldosterone ; Alkalosis ; Angiotensin II ; Angiotensins ; Blood Pressure* ; Catecholamines ; Epithelial Sodium Channels ; Negotiating ; Nephrons ; Rodentia

Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl⁻ absorption and HCO₃⁻ secretion largely through pendrin-dependent Cl⁻/HCO₃⁻ exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO₃ administration. In some rodent models, pendrin-mediated HCO₃⁻ secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl⁻ absorption, but also by modulating the aldosterone response for epithelial Na⁺ channel (ENaC)-mediated Na⁺ absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure.
Absorption ; Acid-Base Equilibrium ; Adrenal Medulla ; Aldosterone ; Alkalosis ; Angiotensin II ; Angiotensins ; Blood Pressure* ; Catecholamines ; Epithelial Sodium Channels ; Negotiating ; Nephrons ; Rodentia

The original version of this article contained misspelled name of authors. The name of Seung-Yeol Na is replaced with Seung-Yeol Nah. The name of Mi-Sung Choi is replaced with Mee-Sung Choi.
Adrenal Medulla*

Orthostatic hypotension (OH) is associated with symptoms including headache, dizziness, and syncope. The incidence of OH increases with age. Attenuation of the vestibulosympathetic reflex (VSR) is also associated with an increased incidence of OH. In order to understand the pathophysiology of OH, we investigated the physiological characteristics of the VSR in the disorder. We applied sodium nitroprusside (SNP) to conscious rats with sinoaortic denervation in order to induce hypotension. Expression of pERK in the intermediolateral cell column (IMC) of the T4~7 thoracic spinal regions, blood epinephrine levels, and blood pressure were evaluated following the administration of glutamate and/or SNP. SNP-induced hypotension led to increased pERK expression in the medial vestibular nucleus (MVN), rostral ventrolateral medullary nucleus (RVLM) and the IMC, as well as increased blood epinephrine levels. We co-administered either a glutamate receptor agonist or a glutamate receptor antagonist to the MVN or the RVLM. The administration of the glutamate receptor agonists, AMPA or NMDA, to the MVN or RVLM led to elevated blood pressure, increased pERK expression in the IMC, and increased blood epinephrine levels. Administration of the glutamate receptor antagonists, CNQX or MK801, to the MVN or RVLM attenuated the increased pERK expression and blood epinephrine levels caused by SNP-induced hypotension. These results suggest that two components of the pathway which maintains blood pressure are involved in the VSR induced by SNP. These are the neurogenic control of blood pressure via the RVLM and the humoral control of blood pressure via epinephrine release from the adrenal medulla.
6-Cyano-7-nitroquinoxaline-2,3-dione ; Adrenal Medulla ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid ; Animals ; Blood Pressure ; Denervation ; Dizocilpine Maleate ; Dizziness ; Epinephrine ; Excitatory Amino Acid Antagonists ; Glutamic Acid ; Headache ; Hypotension* ; Hypotension, Orthostatic ; Incidence ; N-Methylaspartate ; Nitroprusside ; Rats* ; Receptors, Glutamate ; Reflex* ; Spinal Cord Lateral Horn ; Syncope ; Vestibular Nuclei

The present study was designed to investigate the characteristics of gintonin, one of components isolated from Korean Ginseng on secretion of catecholamines (CA) from the isolated perfused model of rat adrenal gland and to clarify its mechanism of action. Gintonin (1 to 30 µg/ml), perfused into an adrenal vein, markedly increased the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. The gintonin-evoked CA secretion was greatly inhibited in the presence of chlorisondamine (1 µM, an autonomic ganglionic bloker), pirenzepine (2 µM, a muscarinic M₁ receptor antagonist), Ki14625 (10 µM, an LPA₁/₃ receptor antagonist), amiloride (1 mM, an inhibitor of Na⁺/Ca²⁺ exchanger), a nicardipine (1 µM, a voltage-dependent Ca²⁺ channel blocker), TMB-8 (1 µM, an intracellular Ca²⁺ antagonist), and perfusion of Ca²⁺-free Krebs solution with 5mM EGTA (a Ca²⁺chelater), while was not affected by sodium nitroprusside (100 µM, a nitrosovasodialtor). Interestingly, LPA (0.3~3 µM, an LPA receptor agonist) also dose-dependently enhanced the CA secretion from the adrenal medulla, but this facilitatory effect of LPA was greatly inhibited in the presence of Ki 14625 (10 µM). Moreover, acetylcholine (AC)-evoked CA secretion was greatly potentiated during the perfusion of gintonin (3 µg/ml). Taken together, these results demonstrate the first evidence that gintonin increases the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. This facilitatory effect of gintonin seems to be associated with activation of LPA- and cholinergic-receptors, which are relevant to the cytoplasmic Ca²⁺ increase by stimulation of the Ca²⁺ influx as well as by the inhibition of Ca²⁺ uptake into the cytoplasmic Ca²⁺ stores, without the increased nitric oxide (NO). Based on these results, it is thought that gintonin, one of ginseng components, can elevate the CA secretion from adrenal medulla by regulating the Ca²⁺ mobilization for exocytosis, suggesting facilitation of cardiovascular system. Also, these findings show that gintonin might be at least one of ginseng-induced hypertensive components.
Acetylcholine ; Adrenal Glands ; Adrenal Medulla* ; Amiloride ; Animals ; Cardiovascular System ; Catecholamines ; Chlorisondamine ; Cytoplasm ; Egtazic Acid ; Exocytosis ; Ganglia, Autonomic ; Nicardipine ; Nitric Oxide ; Nitroprusside ; Panax ; Perfusion ; Pirenzepine ; Rats ; Veins

Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors arising from chromaffin cells in the adrenal medulla. Typical classic triad are consisted of headaches, palpitations, and profuse diaphoresis. But some patients with pheochromocytomas have other cardiovascular manifestations such as left ventricular hypertrophy, congestive heart failure, and cardiac arrhythmia. Rarely, pheochromocytomas manifest as acute myocardial infarction leading to delayed diagnosis and treatment. We experienced one case of pheochromocytoma initially manifesting as acute myocardial infarction which showed normal coronary artery on coronary angiography. Pheochromocytoma should be suspected and evaluated in patients with acute myocardial infarction whose coronary angiography shows normal coronary without definite thrombosis.
Adrenal Medulla ; Arrhythmias, Cardiac ; Chromaffin Cells ; Coronary Angiography ; Coronary Vessels ; Delayed Diagnosis ; Headache ; Heart Failure ; Humans ; Hypertrophy, Left Ventricular ; Myocardial Infarction* ; Neuroendocrine Tumors ; Pheochromocytoma* ; Thrombosis

OBJECTIVETo explore the action mechanism of electroacupuncture (EA) at "Shenmen" (HT 7) and "Sanyinjiao" (SP 6) on insomnia.

METHODSThirty SD rats were randomly divided into a blank group, a model group and an EA group, 10 cases in each group. The insomnia model was made by immobilization method in the model group and EA group. After model establishment, rats in the blank group and model group were treated with fixation and no treatment was given. Rats in the EA group were treated with EA at "Shenmen" (HT 7) and "San-yinjiao" (SP 6) for 15 min, once a day for 4 days. After treatment, the level of daytime and nighttime activity, open-arm entry percentage and open-arm time percentage of elevated plus-maze test were measured; the content of noradrenaline (NE), dopamine (DA) and epinephrine (EPI) in plasma and NE, DA in thalamus and brainstem were detected by using euzymelinked immunosorbent assay method.

RESULTSCompared with the blank group, the daytime activity was increased and nighttime activity was reduced in the model group (both P<0. 05); the open-arm entry percentage and open-arm time percentage of elevated plus-maze test were both reduced in the model group (both P<0. 05); the contents of NE, DA, EPI in the plasma and NE, DA in thalamus and brainstem were increased in the model group (all P<0. 05). Compared with the model group, the daytime activity was reduced and nighttime activity was increased in the EA group (both P<0. 05); the open-arm entry percentage and open-arm time percentage of elevated plus-maze test were both increased in the EA group (both P<0. 05); the contents of NE, DA, EPI in the plasma and NE, DA in thalamus and brainstem were reduced in the EA group (all P< 0. 05).

CONCLUSIONElectroacupuncture at "Shenmen" (HT 7) and "Sanyinjiao" (SP 6) can restrain the over-activity of the sympathetic-adrenal medullary system to treat the insomnia.

Acupuncture Points ; Adrenal Medulla ; metabolism ; Animals ; Anxiety ; Disease Models, Animal ; Dopamine ; metabolism ; Electroacupuncture ; Female ; Humans ; Male ; Norepinephrine ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders ; metabolism ; physiopathology ; psychology ; therapy ; Sympathetic Nervous System ; physiopathology

OBJECTIVE: The vestibular system contributes control of blood pressure during postural changes through the vestibulosympathetic reflex. In the vestibulosympathetic reflex, afferent signals from the peripheral vestibular receptors are transmitted to the vestibular nuclei, rostral ventrolateral medullary nuclei, and then to the intermediolateral cell column of the thoracolumbar spinal cord. Physiological characteristics of the vestibulosympathetic reflex in terms of neurogenic and humoral control of blood pressure were investigated in this study. METHODS: Conscious rats with sinoaortic denervation were used for removal of baroreceptors in reflex control of blood pressure, and hypotension was induced by intravenous infusion of sodium nitroprusside (SNP). Expression of c-Fos protein was measured in the medial vestibular nuclei (MVN), rostral vestrolateral medullary nuclei(RVLM), and intermediolateral cell column (IMC) in T4-7, and levels of blood epinephrine were measured following SNP-induced hypotension. RESULTS: SNP-induced hypotension significantly increased expression of c-Fos protein in the MVN, RVLM, and IMC, also significantly increased level of blood epinephrine compared to normotensive control animals. CONCLUSION: These results suggest that the vestibulosympathetic reflex regulates blood pressure through neurogenic control including MVN, RVLM, and IMC, also through humoral control including epinephrine secretion by the adrenal medulla following SNP-induced hypotension. The physiological characteristics of the reflex may contribute to basic treatment of impairment of blood pressure control during postural changes.
Adrenal Medulla ; Animals ; Blood Pressure ; Denervation ; Epinephrine ; Hypotension ; Infusions, Intravenous ; Nitroprusside ; Pressoreceptors ; Rats ; Reflex ; Spinal Cord ; Vestibular Nuclei

BACKGROUND: The present study was attempted to compare enalapril, an angiotensin-converting enzyme inhibitor with losartan an angiotensin II (Ang II) receptor blocker in the inhibitory effects on the secretion of catecholamines (CA) from the perfused model of the rat adrenal gland. METHODS: The adrenal gland was isolated and perfused with Krebs-bicarbonate. CA was measured directly by using the fluorospectrophotometer. RESULTS: Both enalapril and losartan during perfusion into an adrenal vein for 90 minutes inhibited the CA release evoked by acetylcholine (ACh), 1.1-dimethyl-4-phenyl piperazinium (DMPP, a selective Nn agonist), high K+ (a direct membrane-depolarizer), 3-(m-chloro-phenyl-carbamoyl-oxy-2-butynyl-trimethyl ammonium (McN-A-343, a selective M1 agonist), and Ang II in a time-dependent manner. Also, in the presence of enalapril or losartan, the CA release evoked by veratridine (an activator of voltage-dependent Na+ channels), 6-dimethyl-3-nitro-4-(2-trifluoromethyl-phenyl)-pyridine-5-carboxylate (BAY-K-8644, an L-type Ca2+ channel activator), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor) were significantly reduced. Based on the same concentration of enalapril and losartan, for the CA release evoked by ACh, high K+, DMPP, McN-A-343, Ang II, veratridine, BAY-K-8644, and cyclopiazonic acid, the following rank order of inhibitory potency was obtained: losartan > enalapril. In the simultaneous presence of enalapril and losartan, ACh-evoked CA secretion was more strongly inhibited compared with that of enalapril- or losartan-treated alone. CONCLUSIONS: Collectively, these results demonstrate that both enalapril and losartan inhibit the CA secretion evoked by activation of both cholinergic and Ang II type-1 receptors stimulation in the perfused rat adrenal medulla. When these two drugs were used in combination, their effects were enhanced, which may also be of clinical benefit. Based on concentration used in this study, the inhibitory effect of losartan on the CA secretion seems to be more potent than that of enalapril.
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride ; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; Acetylcholine ; Adrenal Glands ; Adrenal Medulla ; Ammonium Compounds ; Angiotensin II ; Animals ; Catecholamines ; Cytoplasm ; Dimethylphenylpiperazinium Iodide ; Enalapril* ; Losartan* ; Perfusion ; Rats ; Veins ; Veratridine