scholarly journals Effect of heart failure on catecholamine granule morphology and storage in chromaffin cells

2016 ◽  
Vol 230 (3) ◽  
pp. 309-323 ◽  
Author(s):  
Sushil K Mahata ◽  
Hong Zheng ◽  
Sumana Mahata ◽  
Xuefei Liu ◽  
Kaushik P Patel
Keyword(s):  
Heart Failure ◽  
Adrenal Medulla ◽  
Energy Demand ◽  
Chromaffin Cells ◽  
Cell Metabolism ◽  
Dense Core Vesicle ◽  
Synaptic Activation ◽  
Sprague Dawley ◽  
Catecholamine Levels

One of the key mechanisms involved in sympathoexcitation in chronic heart failure (HF) is the activation of the adrenal glands. Impact of the elevated catecholamines on the hemodynamic parameters has been previously demonstrated. However, studies linking the structural effects of such overactivation with secretory performance and cell metabolism in the adrenomedullary chromaffin cells in vivo have not been previously reported. In this study, HF was induced in male Sprague-Dawley rats by ligation of the left coronary artery. Five weeks after surgery, cardiac function was assessed by ventricular hemodynamics. HF rats showed increased adrenal weight and adrenal catecholamine levels (norepinephrine, epinephrine and dopamine) compared with sham-operated rats. Rats with HF demonstrated increased small synaptic and dense core vesicle in splanchnic–adrenal synapses indicating trans-synaptic activation of catecholamine biosynthetic enzymes, increased endoplasmic reticulum and Golgi lumen width to meet the demand of increased catecholamine synthesis and release, and more mitochondria with dilated cristae and glycogen to accommodate for the increased energy demand for the increased biogenesis and exocytosis of catecholamines from the adrenal medulla. These findings suggest that increased trans-synaptic activation of the chromaffin cells within the adrenal medulla may lead to increased catecholamines in the circulation which in turn contributes to the enhanced neurohumoral drive, providing a unique mechanistic insight for enhanced catecholamine levels in plasma commonly observed in chronic HF condition.

High-intensity training induces EIB in rats through neuron transdifferentiation of adrenal medulla chromaffin cells

2013 ◽  
Vol 304 (9) ◽  
pp. L602-L612 ◽  
Author(s):  
Ruoxi He ◽  
Juntao Feng ◽  
Qiufen Xun ◽  
Qingwu Qin ◽  
Chengping Hu
Keyword(s):  
Adrenal Medulla ◽  
Chromaffin Cells ◽  
Cell Structure ◽  
Fold Increase ◽  
Inflammatory Cells ◽  
Whole Body ◽  
Moderate Intensity ◽  
Sprague Dawley ◽  
Exercise Interventions ◽  
Intensity Training

A high prevalence of exercise-induced bronchoconstriction (EIB) can be found in elite athletes, but the underlying mechanisms remain elusive. Airway responsiveness, NGF and epinephrine (EPI) levels, and chromaffin cell structure in high- (HiTr) and moderate-intensity training (MoTr) rats with or without ovalbumin (OVA) sensitization were measured in a total of 120 male Sprague-Dawley rats. The expression of NGF-associated genes in rat adrenal medulla was tested. Both HiTr and OVA intervention significantly increased airway resistance to aerosolized methacholine measured by whole body plethysmography. HiTr significantly increased inflammatory reaction in the lung with a major increase in peribronchial lymphocyte infiltration, whereas OVA significantly increased the infiltration of various inflammatory cells with an over 10-fold increase in eosinophil level in bronchoalveolar lavage. Both HiTr and OVA intervention upregulated circulating NGF level and peripherin level in adrenal medulla, but downregulated phenylethanolamine N-methyl transferase level in adrenal medulla and circulating EPI level. HiTr + OVA and HiTr + ExhEx (exhaustive exercise) interventions significantly enhanced most of the HiTr effects. The elevated NGF level was significantly associated with neuronal conversion of adrenal medulla chromaffin cells (AMCC). The levels of p-Erk1/2, JMJD3, and Mash1 were significantly increased, but the levels of p-p38 and p-JNK were significantly decreased in adrenal medulla in HiTr and OVA rats. Injection of NGF antiserum and moderate-intensity training reversed these changes observed in HiTr and/or OVA rats. Our study suggests that NGF may play a vital role in the pathogenesis of EIB by inducing neuron transdifferentiation of AMCC via MAPK pathways and subsequently decreasing circulating EPI.

THE EFFECTS OF INSULIN, RESERPINE AND CHOLINE 2:6-XYLYLETHER BROMIDE ON THE ADRENAL MEDULLA AND ON MEDULLARY AUTOGRAFTS IN THE RAT

1958 ◽  
Vol 17 (2) ◽  
pp. 191-NP ◽  
Author(s):  
R. E. COUPLAND
Keyword(s):  
Adrenal Medulla ◽  
Intravenous Injection ◽  
Chromaffin Cells ◽  
Sprague Dawley ◽  
Noradrenaline Content ◽  
Single Intravenous Injection ◽  
Catechol Amine ◽  
Amine Content

SUMMARY The adrenaline and noradrenaline content of the adrenal medulla and medullary implants has been assessed by histochemical and assay techniques after the injection of insulin, reserpine, and choline 2:6-xylylether bromide (TM10) into Wistar and Sprague-Dawley strain rats. Insulin hypoglycaemia is without effect on implanted chromaffin cells, but reduces the adrenaline content of the intact adrenal. Reserpine reduces the catechol amine content of both normal and grafted chromaffin cells. TM10, given as a single intravenous injection, has no effect on either normal or implanted chromaffin cells.

scholarly journals Metabolic Aspects of Anthracycline Cardiotoxicity

2021 ◽  
Vol 22 (2) ◽  
Author(s):  
Michele Russo ◽  
Angela Della Sala ◽  
Carlo Gabriele Tocchetti ◽  
Paolo Ettore Porporato ◽  
Alessandra Ghigo
Keyword(s):  
Heart Failure ◽  
Anticancer Agents ◽  
Energy Demand ◽  
Cardiac Metabolism ◽  
Current Evidence ◽  
Anthracycline Cardiotoxicity ◽  
Cardiac Side Effects ◽  
The Impact

Opinion statementHeart failure (HF) is increasingly recognized as the major complication of chemotherapy regimens. Despite the development of modern targeted therapies such as monoclonal antibodies, doxorubicin (DOXO), one of the most cardiotoxic anticancer agents, still remains the treatment of choice for several solid and hematological tumors. The insurgence of cardiotoxicity represents the major limitation to the clinical use of this potent anticancer drug. At the molecular level, cardiac side effects of DOXO have been associated to mitochondrial dysfunction, DNA damage, impairment of iron metabolism, apoptosis, and autophagy dysregulation. On these bases, the antioxidant and iron chelator molecule, dexrazoxane, currently represents the unique FDA-approved cardioprotectant for patients treated with anthracyclines.A less explored area of research concerns the impact of DOXO on cardiac metabolism. Recent metabolomic studies highlight the possibility that cardiac metabolic alterations may critically contribute to the development of DOXO cardiotoxicity. Among these, the impairment of oxidative phosphorylation and the persistent activation of glycolysis, which are commonly observed in response to DOXO treatment, may undermine the ability of cardiomyocytes to meet the energy demand, eventually leading to energetic failure. Moreover, increasing evidence links DOXO cardiotoxicity to imbalanced insulin signaling and to cardiac insulin resistance. Although anti-diabetic drugs, such as empagliflozin and metformin, have shown interesting cardioprotective effects in vitro and in vivo in different models of heart failure, their mechanism of action is unclear, and their use for the treatment of DOXO cardiotoxicity is still unexplored.This review article aims at summarizing current evidence of the metabolic derangements induced by DOXO and at providing speculations on how key players of cardiac metabolism could be pharmacologically targeted to prevent or cure DOXO cardiomyopathy.

scholarly journals OR03-02 Identification of a Novel Stem/Progenitor Population of the Adrenal Medulla

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Alice Santambrogio ◽  
John P Russell ◽  
Emily J Lodge ◽  
Laura D Scriba ◽  
Ilona Berger ◽  
...  
Keyword(s):  
Adrenal Medulla ◽  
Chromaffin Cells ◽  
Cell Types ◽  
Lineage Tracing ◽  
Genetic Lineage ◽  
Outer Cortex ◽  
Differentiation Potential ◽  
Sustentacular Cells

Abstract The adrenal glands regulate multiple physiological processes including the stress response, the immune system and metabolism. The adrenal is composed of an outer cortex that produces steroids, and an inner medulla that produces catecholamines. Tissue-specific stem/progenitor populations have been identified in the adrenal cortex, while the presence of a functional stem/progenitor population in the adrenal medulla is unclear. The adrenal medulla derives from the neural crest and contains chromaffin cells, neurons and sustentacular (support) cells. Establishing cell hierarchy and elucidating mechanisms of regulation of the different cell types is important to understand normal homeostasis and disease pathogenesis, such as of pheochromocytomas. Using genetic approaches in mouse, we have established that a subpopulation of sustentacular cells express the stem/progenitor marker SOX2. Through genetic lineage-tracing using the Sox2-CreERT2 strain, we demonstrate that these are an expanding population, capable of giving rise to chromaffin cells and neurons throughout life, consistent with a stem/progenitor role in vivo. We further demonstrate the self-renewal and differentiation potential of SOX2+ cells through in vitro isolation and expansion. Through analysis of FFPE sections of human adrenals, we confirm the presence of SOX2+ cells in the normal adult organ, as well as in pheochromocytomas. Taken together, our data support the identification of a previously undescribed stem/progenitor cell in the mammalian adrenal medulla, and confirm its functional relevance.

scholarly journals Sympathetic Modulation by Carvedilol and Losartan Reduces Angiotensin II-Mediated Lipolysis in Subcutaneous and Visceral Fat

2005 ◽  
Vol 90 (5) ◽  
pp. 2888-2897 ◽  
Author(s):  
Aderville Cabassi ◽  
Pietro Coghi ◽  
Paolo Govoni ◽  
Elisa Barouhiel ◽  
Ester Speroni ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Advanced Heart Failure ◽  
Ang Ii ◽  
Sympathetic Activation ◽  
Sprague Dawley ◽  
Content Ratio ◽  
Adrenergic Blocker

Advanced heart failure is characterized by increased activation of the renin-angiotensin system and the development of cachexia. Angiotensin II (Ang II) has been proposed as a lipid metabolism regulator. The effects of exogenous Ang II (osmotic minipump, 525 ng/kg/min for 12 d) on interstitial sc glycerol and norepinephrine levels, indexes of lipolysis, and sympathetic activation, respectively, were measured in Sprague Dawley rats by consecutive microdialysis performed in vivo in white adipose tissue. Higher sustained interstitial glycerol and norepinephrine levels were found after 7 and 12 d of Ang II infusion. Triglyceride to DNA content ratio and adipocyte diameter were reduced in sc and visceral (retroperitoneal and epididymal) fat tissues of Ang II-infused rats, whose body weight was lower and blood pressure higher. Losartan, an Ang II receptor 1 blocker, and carvedilol, an α1-nonselective-β1,2,3-adrenergic blocker, but not doxazosin, an α1-selective-adrenergic blocker, lowered glycerol and norepinephrine levels, preventing lipolysis and weight loss. Our results indicate that Ang II stimulates lipolysis in sc and visceral adipocytes by sympathetic activation and β-adrenergic-receptor stimulation. Nonselective-β-adrenergic and Ang II-receptor1 blockade markedly attenuated the rise of norepinephrine, preventing catabolic effects. The metabolic benefits of carvedilol and losartan, in addition to recognized protective cardiovascular effects, may be relevant in cachectic patients with advanced heart failure.

Selective activation of the adrenal medulla during acute bilateral carotid occlusion and its modulation by α-adrenergic receptors in the rat

1983 ◽  
Vol 61 (4) ◽  
pp. 381-387 ◽  
Author(s):  
Michel Bouvier ◽  
Jacques de Champlain
Keyword(s):  
Adrenal Medulla ◽  
Adrenergic Receptors ◽  
Chromaffin Cells ◽  
Carotid Occlusion ◽  
Sympathetic Fiber ◽  
Bilateral Carotid Occlusion ◽  
Sympathoadrenal Activity ◽  
Bilateral Carotid ◽  
Baroreflex Stimulation

The sympathoadrenal activity was studied during baroreflex stimulation in chloralose anesthetized rats. Circulating norepinephrine (NE) and epinephrine (E) levels were used as indices of sympathetic fiber and adrenal medulla activities, respectively, under basal conditions and during a 1-min bilateral carotid occlusion (CO). In vagotomized rats, the CO induced a significant increase in mean arterial pressure (MAP) associated with an increase in circulating E levels, while this procedure did not alter blood pressure or circulating NE or E levels in intact animals. Following vagotomy, the baroreflex stimulation activated specifically the adrenal medulla, without alteration of the sympathetic fiber activity since the NE levels were not modified by the occlusion. Moreover, in support of that hypothesis, chemical sympathectomy did not decrease the pressure response to CO while bilateral adrenalectomy almost completely abolished this response. The elevation of circulating E induced by the CO was greatly potentiated by pretreatment with Yohimbine, a selective α2-antagonist, and was completely abolished by administration of Clonidine, an α2-agonist, while phenoxybenzamine, which is mainly an α1-antagonist, did not potentiate significantly the E response to CO. These results therefore suggest that the baroreflex activation of the adrenal medulla induced by CO may be modulated in vivo via α2-adrenergic receptors that could be localized on chromaffin cells.

Effects of Ca2+ channel antagonists on acetylcholine and catecholamine releases in the in vivo rat adrenal medulla

2004 ◽  
Vol 287 (1) ◽  
pp. R161-R166 ◽  
Author(s):  
Tsuyoshi Akiyama ◽  
Toji Yamazaki ◽  
Hidezo Mori ◽  
Kenji Sunagawa
Keyword(s):  
Adrenal Medulla ◽  
Nerve Stimulation ◽  
Chromaffin Cells ◽  
Splanchnic Nerve ◽  
Ringer Solution ◽  
Norepinephrine Release ◽  
Ach Release ◽  
Before And After ◽  
Voltage Dependent

To elucidate the types of voltage-dependent Ca2+ channels controlling ACh and catecholamine releases in the in vivo adrenal medulla, we implanted microdialysis probes in the left adrenal medulla of anesthetized rats and investigated the effects of Ca2+ channel antagonists on ACh, norepinephrine, and epinephrine releases induced by nerve stimulation. The dialysis probes were perfused with Ringer solution containing a cholinesterase inhibitor, neostigmine. The left splanchnic nerves were electrically stimulated at 2 and 4 Hz before and after intravenous administration of Ca2+ channel antagonists. ω-Conotoxin GVIA (an N-type Ca2+ channel antagonist, 10 μg/kg) inhibited ACh release at 2 and 4 Hz by ∼40%, norepinephrine release at 4 Hz by ∼50%, and epinephrine release at 2 and 4 Hz by ∼45%. A fivefold higher dose of ω-conotoxin GVIA (50 μg/kg) did not further inhibit these releases. ω-Conotoxin MVIIC (a P/Q-type Ca2+ channel antagonist, 50 μg/kg) inhibited ACh and epinephrine releases at 4 Hz by ∼30%. Combined ω-conotoxin GVIA (50 μg/kg) and MVIIC (250 μg/kg) inhibited ACh release at 2 and 4 Hz by ∼70% and norepinephrine and epinephrine releases at 2 and 4 Hz by ∼80%. Nifedipine (an L-type Ca2+ channel antagonist, 300 and 900 μg/kg) did not change ACh release at 2 and 4 Hz; however, nifedipine (300 μg/kg) inhibited epinephrine release at 4 Hz by 20%, and nifedipine (900 μg/kg) inhibited norepinephrine and epinephrine releases at 4 Hz by 30%. In conclusion, both N- and P/Q-type Ca2+ channels control ACh release on preganglionic splanchnic nerve endings while L-type Ca2+ channels do not. L-type Ca2+ channels are involved in norepinephrine and epinephrine releases on chromaffin cells.

Sinusoidal Cells in Bone Marrow Take Up BSA-Au Conjugates in the Presence of an Artificial Blood Substitute

1985 ◽  
Vol 43 ◽  
pp. 700-701
Author(s):  
J.S. Geoffroy ◽  
R.P. Becker
Keyword(s):  
Bone Marrow ◽  
Los Angeles ◽  
Iliac Artery ◽  
Blood Substitute ◽  
Sprague Dawley ◽  
Coated Pits ◽  
Sinusoidal Cells ◽  
Artificial Blood ◽  
Left Common Iliac Artery

The pattern of BSA-Au uptake in vivo by endothelial cells of the venous sinuses (sinusoidal cells) of rat bone marrow has been described previously. BSA-Au conjugates are taken up exclusively in coated pits and vesicles, enter and pass through an “endosomal” compartment comprised of smooth-membraned tubules and vacuoles and cup-like bodies, and subsequently reside in multivesicular and dense bodies. The process is very rapid, with BSA-Au reaching secondary lysosmes one minute after presentation. (Figure 1)In further investigations of this process an isolated limb perfusion method using an artificial blood substitute, Oxypherol-ET (O-ET; Alpha Therapeutics, Los Angeles, CA) was developed. Under nembutal anesthesia, male Sprague-Dawley rats were laparotomized. The left common iliac artery and vein were ligated and the right iliac artery was cannulated via the aorta with a small vein catheter. Pump tubing, preprimed with oxygenated 0-ET at 37°C, was connected to the cannula.

Preparation of cultured astrocytes for x-ray microanalysis

1989 ◽  
Vol 47 ◽  
pp. 988-989
Author(s):  
N.K.R. Smith ◽  
K.E. Hunter ◽  
P. Mobley ◽  
L.P. Felpel
Keyword(s):  
Cultured Cells ◽  
Elemental Content ◽  
Elemental Distribution ◽  
Sprague Dawley ◽  
X Ray ◽  
Cultured Astrocytes ◽  
Freeze Dried ◽  
Ultimate Objective

Electron probe energy dispersive x-ray microanalysis (XRMA) offers a powerful tool for the determination of intracellular elemental content of biological tissue. However, preparation of the tissue specimen , particularly excitable central nervous system (CNS) tissue , for XRMA is rather difficult, as dissection of a sample from the intact organism frequently results in artefacts in elemental distribution. To circumvent the problems inherent in the in vivo preparation, we turned to an in vitro preparation of astrocytes grown in tissue culture. However, preparations of in vitro samples offer a new and unique set of problems. Generally, cultured cells, growing in monolayer, must be harvested by either mechanical or enzymatic procedures, resulting in variable degrees of damage to the cells and compromised intracel1ular elemental distribution. The ultimate objective is to process and analyze unperturbed cells. With the objective of sparing others from some of the same efforts, we are reporting the considerable difficulties we have encountered in attempting to prepare astrocytes for XRMA.Tissue cultures of astrocytes from newborn C57 mice or Sprague Dawley rats were prepared and cultured by standard techniques, usually in T25 flasks, except as noted differently on Cytodex beads or on gelatin. After different preparative procedures, all samples were frozen on brass pins in liquid propane, stored in liquid nitrogen, cryosectioned (0.1 μm), freeze dried, and microanalyzed as previously reported.

Immunogold labeling of the calcium binding protein synexin in isolated adrenal chromaffin granules and chromaffin cells

1990 ◽  
Vol 48 (3) ◽  
pp. 952-953
Author(s):  
Gemma A.J. Kuijpers ◽  
Harvey B. Pollard
Keyword(s):  
Adrenal Medulla ◽  
Calcium Binding ◽  
Chromaffin Cells ◽  
Cell Activation ◽  
Structural Information ◽  
Dependent Manner ◽  
Chromaffin Granules ◽  
Immuno Electron Microscopy ◽  
Ultrathin Sections ◽  
Adrenal Chromaffin

Exocytotic fusion of granules in the adrenal medulla chromaffin cell is triggered by a rise in the concentration of cytosolic Ca2+ upon cell activation. The protein synexin, annexin VII, was originally found in the adrenal medulla and has been shown to cause aggregation and to support fusion of chromaffin granules in a Ca2+-dependent manner. We have previously suggested that synexin may there fore play a role in the exocytotic fusion process. In order to obtain more structural information on synexin, we performed immuno-electron microscopy on frozen ultrathin sections of both isolated chromaffin granules and chromaffin cells.Chromaffin granules were isolated from bovine adrenal medulla, and synexin was isolated from bovine lung. Granules were incubated in the presence or absence of synexin (24 μg per mg granule protein) and Ca2+ (1 mM), which induces maximal granule aggregation, in 0.3M sucrose-40m MMES buffer(pH 6.0). Granules were pelleted, washed twice in buffer without synexin and fixed with 2% glutaraldehyde- 2% para formaldehyde in 0.1 M phosphate buffer (GA/PFA) for 30 min. Chromaffin cells were isolated and cultured for 3-5 days, and washed and incubated in Krebs solution with or without 20 uM nicotine. Cells were fixed 90 sec after on set of stimulation with GA/PFA for 30 min. Fixed granule or cell pellets were washed, infiltrated with 2.3 M sucrose in PBS, mounted and frozen in liquid N2.

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