Increased Plasma Catecholamine Levels Research Articles

Relation of Plasma Catecholamine Concentrations and Myocardial Mitochondrial Respiratory Activity in Anesthetized and Mechanically Ventilated, Cardiovascular Healthy Swine.

Chronic heart failure is associated with reduced myocardial β-adrenergic receptor expression and mitochondrial function. Since these data coincide with increased plasma catecholamine levels, we investigated the relation between myocardial β-receptor expression and mitochondrial respiratory activity under conditions of physiological catecholamine concentrations. This post hoc analysis used material of a prospective randomized, controlled study on 12 sexually mature (age 20-24 weeks) Early Life Stress or control pigs (weaning at day 21 and 28-35 after birth, respectively) of either sex. Measurements in anesthetized, mechanically ventilated, and instrumented animals comprised serum catecholamine (liquid-chromatography/tandem-mass-spectrometry) and 8-isoprostane levels, whole blood superoxide anion concentrations (electron spin resonance), oxidative DNA strand breaks (tail moment in the "comet assay"), post mortem cardiac tissue mitochondrial respiration, and immunohistochemistry (β2-adrenoreceptor, mitochondrial respiration complex, and nitrotyrosine expression). Catecholamine concentrations were inversely related to myocardial mitochondrial respiratory activity and β2-adrenoceptor expression, whereas there was no relation to mitochondrial respiratory complex expression. Except for a significant, direct, non-linear relation between DNA damage and noradrenaline levels, catecholamine concentrations were unrelated to markers of oxidative stress. The present study suggests that physiological variations of the plasma catecholamine concentrations, e.g., due to physical and/or psychological stress, may affect cardiac β2-adrenoceptor expression and mitochondrial respiration.

Atrial Fibrillation Detected After Acute Ischemic Stroke

Atrial fibrillation (AF) increases 4-5 times incidence of cardiac embolic stroke. In contrast, as many as 70% of AF cases can be detected in stroke within three days of onset, and this can affect the patient's prognosis. This case report describes the causal pathophysiology of AF and acute stroke and identifies the associated risk factors. Case 1 is a 44-year-old woman, acute stroke with acute decrease level of consciousness. The patient came with status epilepticus and a hypertensive emergency. Obtained a history of stroke, uncontrolled hypertension, and myocardial infarction. Initial Score National Institutes of Health Stroke Scale (NIHSS) was 33 and CHA2DS2-VASc was 5. Investigation non-contrast head Computed Tomography (CT) scan showed no bleeding and echocardiography (ECG) showed AF with rapid ventricular response. The patient died after 3 days of treatment. Case 2 is an 83-year-old woman, acute stroke with acute decrease level of consciousness and right motor lateralization. There was a history of hypertension and stroke with left hemiparesis. The initial NIHSS was 28 and CHA2DS2-VASc was 6. Investigations non-contrast head CT scan showed no bleeding and ECG showed AF with normal ventricular response. The patient was discharged from the hospital after being treated for 22 days with NIHSS of 20. Several risk factors for post-stroke AF are elderly, hypertension, subtype of ischemic stroke, prior stroke, and comorbidities such as DM and hypertension. Post-stroke AF can occur because of changes in heart rhythm through autonomic disorders, increased plasma catecholamine levels, and inflammatory reactions. Early Recognition of risk factors, focusing on patients at higher risk of AF detected after stroke becomes important for comprehensive management of stroke with AF.
 Keywords: acute ischemic stroke, atrial fibrillation, CHA2DS2-VASc score, risk factors.

Astrocytes in the PVN are involved in corticotropin-releasing factor-induced sympathetic activation in rats

Corticotropin-releasing factor (CRF) plays a key role in stress responses in the brain. CRF activates not only the hypothalamic-pituitary-adrenal axis but also the sympathetic nervous system. We previously reported that both central administration of CRF and exposure to acute restraint stress (RS) increase plasma catecholamine levels and activate presympathetic neurons in the paraventricular hypothalamic nucleus (PVN). However, it is unclear whether glial cells in brain regions including the PVN are involved in CRF- or stress-induced sympathetic activation. In this study, we examined roles of astrocytes in the CRF-induced elevation of plasmas catecholamine levels (noradrenaline and adrenaline) using fluorocitrate which blocks glial metabolic function. Intracerebroventricular pretreatment of fluorocitrate suppressed the CRF-induced elevation of plasma levels of noradrenaline and adrenaline. On the other hand, microinjection of fluorocitrate into the PVN suppressed the CRF-induced elevation of adrenaline, but not of noradrenaline. Furthermore, we tried to examine effects of inhibition of astrocytes on RS-induced sympathetic activation. Our results suggest that astrocytic function in the brain is important for the CRF-induced sympathetic activation and the effects might be brain region-dependent.

The effect of endotracheal aspiration on QT interval in intensive care unit patients

Objective: The intensive care unit (ICU) environment and applied methods may lead to a significant stimulation of sympathoadrenal activity. There are studies about the direct connection between increased plasma catecholamine levels during sympathetic activation and QT interval. Therefore, the aim of this study is to determine the effects of endotracheal aspiration on QT interval and QT dispersion. Method: 90 patients connected to a mechanical ventilator from the ages of 30-70 in ICU were taken into study. Patients taking any drug that prolongs QT, patients with unstable hemodynamia and congenital QT prolongation were excluded. Preoxygenation was done to all patients with 100% O 2 administration for 1 minute before the endotracheal aspiration (ET). Age, diagnosis, weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), peripheral oxygen saturation (SpO 2 ), QT, QTc, Glasgow Coma Score (GCS) values were recorded before, during, 5 minutes after and 10 minutes after the ET aspiration. Results: During ET aspiration, the mean QTc value was 445.1±23.0 milliseconds (ms), the mean QT value was 379.2 ± 19.3 ms. In 14% of the patients included in the study, basal QTc values above 420 ms were found to be prolonged. According to basal values, QT and QTc intervals were prolonged in almost all patients during, 5 minutes after and 10 minutes after the ET aspiration. Conclusions: QT interval prolongation should always be checked by calculating corrected QT interval, and ICU physicians need to be more careful in patients with coronary heart disease and congenital prolonged QT interval in terms of fatal ventricular arrhythmias.

Use of desflurane during anesthesia for resection of extra-adrenal pheochromocytoma: a case report

BackgroundAlthough various agents are used during anesthesia for surgical resection of pheochromocytoma, application of desflurane has rarely been reported. We report the use of desflurane in a case receiving resection of extra-adrenal pheochromocytoma.Case presentationA 51-year-old female was transferred to our hospital for sustained hypertension. A diagnosis of extra-adrenal pheochromocytoma was made based on increased plasma catecholamine levels and radiographic findings. Surgical resection was planned after controlling blood pressure. General anesthesia was induced with propofol and fentanyl, followed by maintenance with desflurane 4.3% and remifentanil 0.2–0.4 μg/kg/min. Blood pressure and heart rate were stable during induction, tracheal intubation, and tumor manipulation. Blood pressure abruptly decreased to 62/40 mmHg after removal of the tumor, which was treated with noradrenaline. The surgery was completed uneventfully and the postoperative course was also uneventful.ConclusionDesflurane was safely used in combination with remifentanil during anesthesia for resection of extra-adrenal pheochromocytoma.

Giant cystic pheochromocytoma masquerading as acute coronary syndrome and transient left ventricular dysfunction: a case report

Objective of present study to present an atypical manifestation of pheochromocytoma and to illustrate the difficulty in managing an acute coronary syndrome and left ventricular dysfunction during a hypertensive crisis attributable to pheochromocytoma. We present the clinical history, physical findings, lab results and imaging studies of a 62year old man with acute coronary syndrome later found to have an adrenal mass. A 62-year-old man was suspected of having myocardial ischemia on the basis of symptoms of paroxysmal chest discomfort, diaphoresis, ST-segment elevation on an electrocardiogram, and elevated levels of cardiac enzymes. Coronary CT angiography was normal. Echocardiography revealed substantial ballooning of the apical, anterior, and inferior cardiac walls, consistent with catecholamine induced cardiomyopathy. He had a history of labile hypertension, headache, diaphoresis and palpitations of 4 years' duration. A right adrenal mass detected on Magnetic resonance imaging and increased plasma catecholamine levels were consistent with a pheochromocytoma. Treatment with prazosin and labetalol was initiated, and he underwent a right adrenalectomy, which confirmed thepheochromocytoma. Pheochromocytomas must be considered in the setting of acute coronary syndrome especially with presence of labile blood pressure. Inadvertent fibrinolysis can be avoided with proper clinical suspicion and timely coronary imaging.

Differential regulation of catecholamine synthesis and transport in rat adrenal medulla by fluoxetine treatment.

We have recently shown that chronic fluoxetine treatment acted significantly increasing plasma norepinephrine and epinephrine concentrations both in control and chronically stressed adult male rats. However, possible effects of fluoxetine on catecholamine synthesis and re-uptake in adrenal medulla have been largely unknown. In the present study the effects of chronic fluoxetine treatment on tyrosine hydroxylase, a rate-limiting enzyme in catecholamine synthesis, as well as a norepinephrine transporter and vesicular monoamine transporter 2 gene expressions in adrenal medulla of animals exposed to chronic unpredictable mild stress (CUMS) for 4 weeks, were investigated. Gene expression analyses were performed using a real-time quantitative reverse transcription-PCR. Chronically stressed animals had increased tyrosine hydroxylase mRNA levels and decreased expression of both transporters. Fluoxetine increased tyrosine hydroxylase and decreased norepinephrine transporter gene expression in both unstressed and CUMS rats. These findings suggest that chronic fluoxetine treatment increased plasma catecholamine levels by affecting opposing changes in catecholamine synthesis and uptake.

Plasma catecholamine levels before and after paroxetine treatment in patients with panic disorder

Catecholamines such as norepinephrine, epinephrine, and dopamine are closely related to the autonomic nervous system, suggesting that panic disorder may involve elevated catecholamine levels. This study investigated basal and posttreatment catecholamine levels in patients with panic disorder. A total of 29 patients with panic disorder and 23 healthy controls participated in the study. Panic disorder patients received paroxetine treatment for 12 weeks after clinical tests and examination had been conducted. We investigated the difference in basal levels of catecholamine and measured the changes in catecholamine levels before and after drug treatment in panic disorder patients. The basal plasma epinephrine (48.87±6.18pg/ml) and dopamine (34.87±3.57pg/ml) levels of panic disorder patients were significantly higher than those (34.79±4.72pg/ml and 20.40±3.53pg/ml) of the control group. However, basal plasma norepinephrine levels did not show statistically significant differences between patients and controls. After drug therapy, plasma catecholamine levels were nonsignificantly decreased and norepinephrine levels showed a tendency toward a decrease that did not reach significance. In conclusion, this study suggests the possibility of a baseline increase of plasma catecholamine levels and activation of sympathetic nervous systems in patients with panic disorder which may normalize after treatment with paroxetine.

Prevention of cardiac events caused by surgical stress in aged rats: simultaneously activating β2-adrenoceptor and inhibiting β1-adrenoceptor

Increased plasma catecholamine levels are associated with a high risk of perioperative cardiac events in aged individuals undergoing non-cardiac surgical interventions. Given the different effects of β1-adrenoreceptor (β1AR) and β2-adrenoreceptor (β2AR) stimulation by catecholamine in cardiomyocytes, this study evaluated whether simultaneous inhibition of β1AR and activation of β2AR is better than separate application in reducing the risk of perioperative cardiac events in aged rats undergoing non-cardiac surgery. Male aged Sprague–Dawley (SD) rats were divided into five groups. Normal group received no treatment. Surgery group received an abdominal surgery with hypoxia. group, group and group received surgery and hypoxia with metoprolol (100 mg/kg·d), fenoterol (250 μg/kg·d) or both, respectively. The drugs were given three days before surgery with treatment continued through post-surgical day 7. The results showed that simultaneous activation of β2AR with a β2AR agonist and inhibition of β1AR with a selective β1AR blocker normalized myocardial oxygen consumption, decreased myocardial damage, augmented cardiomyocyte survival, improved cardiac function, reduced the incidence of arrhythmia, thus decreasing the occurrence of cardiac events in perioperative aged rats undergoing non-cardiac surgery. The results demonstrated that combined use of β2AR agonist and β1AR blocker achieved better general effects than use of either one alone. Our results provide a new insight into preventing perioperative cardiac events for elderly patients undergoing surgical stress.

Multitracer PET imaging of bone metastases from paraganglioma: peripheral halo of uptake on 18F-FLT PET mismatching with central uptake of 18F-FDOPA, 18F-fluorodopamine, and 18F-FDG

A 70-year-old man with a history of a right adrenal paraganglioma (24 cm) surgically removed 2 years before was referred for lower back pain, palpitations, and increased plasma catecholamine levels suspicious for recurrent paraganglioma. The patient underwent a multi-tracer PET imaging evaluation consisting of four different radiopharmaceuticals, each performed on different days in the same week: 18F-Fdopamine and 18F-FDOPA to specifically detect the presence of paraganglioma [1], 18F-FDG to assess glycolytic activity, and 18F-fluorothymidine (18F-FLT) to assess cell proliferation [2]. The scans revealed retroperitoneal masses, bilateral lung lesions, and bone lesions, with high and variable avidity for 18F-Fdopamine (A), 18F-FDOPA (B), and 18F-FDG (C). The inter-lesion and inter-tracer tracer avidity variability illustrates the metastatic metabolic heterogeneity. All lesions had low 18F-FLT uptake (D), suggesting a low rate of cellular proliferation. However, the bone lesions (green arrows) showed an interesting pattern on 18F-FLT PET. High 18F-FLT uptake is known to occur in normal bone, due to hematopoietic cells in the bone marrow compartment that are continually replacing circulating peripheral blood cells and are highly proliferative [3]. In this patient, bone lesions detected and delineated by T2-weighted MRI (E) and CT (F) showed low cellular proliferation, contrasting with their high catecholamine metabolism and high glycolytic activity. High non-specific peri-tumoral 18F-FLT uptake was seen (higher than the normal bone), most likely corresponding to the reactive proliferation of hematopoietic cells around the lesion. This should elicit caution when interpreting focal uptake (higher than the constitutively high bone marrow background uptake) of 18F-FLT in bone.

Abstract 56: Association between Increased Plasma Catecholamine Levels and Neurogenic Pulmonary Edema in Patients with Subarachnoid Hemorrhage

Background: Neurogenic pulmonary edema (NPE) occurs relatively frequently after aneurysmal subarachnoid hemorrhage (SAH), and excessive release of catecholamines (epinephrine/norepinephrine) has been indicated as its principal cause. The objective of this study is to evaluate the relative contribution of each catecholamine in pathogenesis of NPE. Methods: Records of 77 SAH patients (23 men/54 women) whose plasma catecholamine levels were measured within 48 h of SAH onset were retrospectively analyzed. Results: Eight patients (10%) were diagnosed with NPE. Plasma epinephrine (366.9±347.4 vs. 130.3±167.4 pg/mL, p =0.001) and norepinephrine (3481.1±1678.9 vs. 835.5±688.9 pg/mL, p <0.001) levels were significantly higher in the NPE+ group than NPE- group. Demographic comparison revealed that the severity of SAH and cardiac damage/dysfunction was significantly more profound in the NPE+ group. Multivariate logistic regression analysis revealed that increased norepinephrine levels were predictive of NPE (OR, 1.002; 95% CI, 1.001-1.004), but epinephrine levels were not. Linear regression analysis showed that plasma epinephrine and norepinephrine levels were positively correlated. Receiver operating characteristic (ROC) curves showed that threshold values predictive of NPE existed for both catecholamines, and sensitivity/specificity was higher for norepinephrine. After quadrichotomization of patients based on the results of ROC curves, patients whose plasma epinephrine/norepinephrine levels exceeded the threshold values were significantly more likely to experience NPE. Conclusions: Norepinephrine rather than epinephrine appears to play a more active role in pathogenesis of SAH-induced NPE, although both catecholamines may be involved. Since the number of SAH patients complicated by NPE is relatively small, a multi-center study may be required to clarify the issue.

Reversal of subcellular remodelling by losartan in heart failure due to myocardial infarction

This study tested the reversal of subcellular remodelling in heart failure due to myocardial infarction (MI) upon treatment with losartan, an angiotensin II receptor antagonist. Twelve weeks after inducing MI, rats were treated with or without losartan (20 mg/kg; daily) for 8 weeks and assessed for cardiac function, cardiac remodelling, subcellular alterations and plasma catecholamines. Cardiac hypertrophy and lung congestion in 20 weeks MI-induced heart failure were associated with increases in plasma catecholamine levels. Haemodynamic examination revealed depressed cardiac function, whereas echocardiographic analysis showed impaired cardiac performance and marked increases in left ventricle wall thickness and chamber dilatation at 20 weeks of inducing MI. These changes in cardiac function, cardiac remodelling and plasma dopamine levels in heart failure were partially or fully reversed by losartan. Sarcoplasmic reticular (SR) Ca2+-pump activity and protein expression, protein and gene expression for phospholamban, as well as myofibrillar (MF) Ca2+-stimulated ATPase activity and α-myosin heavy chain mRNA levels were depressed, whereas β-myosin heavy chain expression was increased in failing hearts; these alterations were partially reversed by losartan. Although SR Ca2+-release activity and mRNA levels for SR Ca2+-pump were decreased in failing heart, these changes were not reversed upon losartan treatment; no changes in mRNA levels for SR Ca2+-release channels were observed in untreated or treated heart failure. These results suggest that the partial improvement of cardiac performance in heart failure due to MI by losartan treatment is associated with partial reversal of cardiac remodelling as well as partial recovery of SR and MF functions.

Effects of propiverine hydrochloride, an anticholinergic agent, on urethral continence mechanisms and plasma catecholamine concentration in rats

Anticholinergics are used to treat overactive bladder. Anticholinergic agents such as propiverine hydrochloride reportedly increase plasma catecholamine levels in rats. It is also known that active urethral closure mechanisms prevents stress urinary incontinence (SUI), which is enhanced by central and peripheral noradrenergic system activation. Therefore, we examined the influence of propiverine hydrochloride on urethral anti-incontinence function in rats. Adult female rats were divided into propiverine and vehicle-treated groups. The propiverine group was given propiverine orally once a day for 2 weeks, after which urethral function and plasma concentrations of catecholamine (dopamine, norepinephrine, epinephrine) were tested. Urethral baseline pressure measured by a microtransducer-tipped urethral catheter and leak-point pressure during passive intravesical pressure elevation were significantly increased in the propiverine group compared with the vehicle group. Plasma norepinephrine and epinephrine levels in the propiverine group were also significantly increased. Propiverine treatment that increases plasma catecholamine levels could contribute to improvement of SUI conditions by increasing urethral resistance.

Influence of acute stress on cardiac electrophysiological stability in male goats

Objective Stress plays an important role in the pathogenesis of ventricular arrhythmias. This study was designed to examine the effect of acute stress and metoprolol, a beta adrenergic receptor blocker, on cardiac electrophysiological stability of male goats.Methods Fifteen male goats were randomly divided into three groups: (i) control animals (n = 5), (ii) a compound stimuli group including noise and red flash (n = 5), (iii) and a compound stimuli group with metoprolol treatment (n = 5). Plasma catecholamines were determined by using high performance chromatography with electrochemical detection. Heart rate turbulence (HRT) and heart rate variability (HRV) were analysed with the MGY-H12L analysis system. Also, the ventricular fibrillation threshold (VFT) and the ventricular vulnerable period (VVP) were determined by programmed S1S2 stimulus with bipolar electrodes at the apex of the goat hearts.Results Compound stimuli increased plasma catecholamine levels progressively and decreased the negative value of turbulence onset (TO), turbulence slope (TS), SDNN, PNN50. Moreover, compound stimuli broadened VVP and decreased VFT significantly. Although metoprolol treatment failed to affect plasma catecholamine levels, TS and PNN50 value of the compound stimuli group, it significantly increased the negative value of TO, SDNN, VFT and narrowed VVP.Conclusion Our data demonstrates that compound stimuli can induce acute stressful reactions, and decrease the cardiac electrophysiological stability of male goats, which can be counteracted by metoprolol treatment.

Efficacy of propiverine, an anticholinergic agent, in young and old rats

Aims We examined the influence of propiverine hydrochloride, an anticholinergic agent, on the micturition reflex, blood pressure, and plasma catecholamine levels in young rats and old rats. Main method Male F344/DuCrlCrlj Fischer rats (young rats aged 2 months and old rats aged 26 months) were divided into the following 4 groups: a young sham group, an old sham group, a young propiverine group, and an old propiverine group. Rats from the young (body weight: 215 ± 7 g) or old propiverine groups (body weight: 414 ± 22 g) were administered propiverine hydrochloride (5 or 10 mg, respectively) dissolved in distilled water (0.5 mL) into the stomach through a fine catheter once daily. Rats from the young and old sham groups were administered the same volume of distilled water. After 2 weeks of treatment, continuous cystometry was done with physiological saline and 0.1% acetic acid, and measurement of plasma catecholamines, blood pressure, and heart rate was performed. Key findings The old rats had a longer interval between bladder contractions and higher plasma catecholamine levels than the young rats. Bladder stimulation by 0.1% acetic acid induced frequency in both young and old rats. Administration of propiverine inhibited the induction of frequency in the old rats, but not in the young rats. Propiverine increased plasma catecholamine levels in the young rats, but not in the old rats. Significance These findings show that bladder activity varies with aging, and the response to propiverine also changes in an age-related manner.

The induction of mild hypothermia improves systolic function of the resuscitated porcine heart at no further sympathetic activation

Mild hypothermia (MH) after cardiac arrest attenuates hypoxic brain injury and improves survival. As MH increases contractility in normal hearts, we hypothesized that MH improves cardiovascular function after cardiac arrest. In 16 anaesthetized pigs (64 ± 2 kg), ventricular fibrillation was induced electrically for 5 min. At 10 min after resuscitation and return of spontaneous circulation (ROSC), pigs were assigned to normothermia (NT, 38°C, n = 8) or MH (33°C, n = 8, intravascular cooling). At ROSC 6 h vs. baseline, heart rate (HR) was unchanged in NT, but decreased in MH. Cardiac output (CO, l min(-1)) decreased in MH (3.5 ± 0.2 vs. 5.5 ± 0.4, P < 0.05) more than in NT (4.8 ± 0.4 vs. 5.7 ± 0.4, P = ns). Mixed venous oxygen saturation decreased in NT (56 ± 2 vs. 66 ± 3%, P < 0.05), but remained constant in MH (64 ± 2 vs. 65 ± 2%) due to a 35% decrease of whole body oxygen consumption. Left ventricular (LV) dP/dt(max) (mmHg s(-1)) decreased in NT (1163 ± 97 vs. 1665 ± 134, P < 0.05), but was preserved in MH (1602 ± 102 vs. 1603 ± 96), whereas LV relaxation was profoundly slowed during MH. Pressure-volume analysis confirmed improved LV systolic function during MH, but also demonstrated decreased LV end-diastolic distensibility, which was further potentiated by right atrial pacing at baseline HR. MH did not increase plasma catecholamine levels. Spectral analysis of heart rate variability revealed reduced sympathetic activation during MH. The induction of MH after cardiac resuscitation improves systolic myocardial function without further sympathetic activation. A reduced metabolism during MH outweighs a decreased CO and thereby acts favourably on systemic oxygen supply/demand balance.

Renalase deficiency aggravates ischemic myocardial damage

Chronic kidney disease (CKD) leads to an 18-fold increase in cardiovascular complications not fully explained by traditional risk factors. Levels of renalase, a recently discovered oxidase that metabolizes catecholamines, are decreased in CKD. Here we show that renalase deficiency in a mouse knockout model causes increased plasma catecholamine levels and hypertension. Plasma blood urea nitrogen, creatinine, and aldosterone were unaffected. However, knockout mice had normal systolic function and mild ventricular hypertrophy but tolerated cardiac ischemia poorly and developed myocardial necrosis threefold more severe than that found in wild-type mice. Treatment with recombinant renalase completely rescued the cardiac phenotype. To gain insight into the mechanisms mediating this cardioprotective effect, we tested if gene deletion affected nitrate and glutathione metabolism, but found no differences between hearts of knockout and wild-type mice. The ratio of oxidized (NAD) to reduced (NADH) nicotinamide adenine dinucleotide in cardiac tissue, however, was significantly decreased in the hearts of renalase knockout mice, as was plasma NADH oxidase activity. In vitro studies confirmed that renalase metabolizes NADH and catecholamines. Thus, renalase plays an important role in cardiovascular pathology and its replacement may reduce cardiac complications in renalase-deficient states such as CKD.

Chronic Individual Housing-Induced Stress Decreased Expression of Catecholamine Biosynthetic Enzyme Genes and Proteins in Spleen of Adult Rats

Objective: Social isolation is regarded as one of the most relevant causes of diseases in mammalian species. The activation of the sympathoneural system represents one of the key components of the stress response. The sympathetic nervous system is one of the major pathways involved in immune-neuroendocrine interactions. The aim of the present study was to determine plasma epinephrine and norepinephrine in individually housed rats, as well as to find out whether splenic gene expression of catecholamine synthesizing enzymes and their protein levels are affected by chronic psychosocial stress. Methods: Tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) mRNA levels were quantified by quantitative real-time RT-PCR. The TH, DBH and PNMT immunoproteins were assayed by Western blot. Results: Chronic social isolation of adult male rats produced a significant increase in plasma catecholamine levels and a decrease in splenic TH mRNA, DBH mRNA and PNMT mRNA. Protein levels of TH, DBH and PNMT were also reduced. Conclusion: These results suggest that increased plasma catecholamines and decreased gene expression and protein levels of catecholamine biosynthetic enzymes in the spleen of chronically individually housed animals might reduce catecholamine synthesis, thus leaving the immunocompetent tissues depleted of catecholamines and consequently leading to an impairment of immune response.

Assessment of the Biological Similarity of Three Capsaicin Analogs (Capsinoids) Found in Non-Pungent Chili Pepper (CH-19 Sweet) Fruits

CH-19 Sweet is a newly found chili pepper breed bearing much less pungent fruits. Because CH-19 Sweet fruits were found to contain three analogs (capsinoids) of capsaicin, a major component of pungency of hot peppers (the analogs are capsiate or CST, dihydrocapsiate or DCT, and nordihydrocapsiate or NDCT), we assessed in this study the bio-potencies of these three capsinoids by comparing them with capsaicin. The three capsinoids bound to transient potential vanilloid 1 (TRPV1) receptors expressed in cultured cells and activated Ca(2+) influx in a concentration-dependent manner with similar magnitudes. In contrast to capsaicin, capsinoids at the same concentration induced virtually no nociceptive responses when applied to the eyes or the oral cavities of mice. Intravenous administration of capsaicin or 20-fold increased doses of each capsinoid to rats induced significant increases in plasma catecholamine levels. Orally administered, each capsinoid enhanced oxygen consumption in mice. Based on the present results, capsaicin and these three capsinoids should have similar bio-potency, though capsinoids do not generate pungency or sensory irritation.

Activation of the sympathoadrenal system in rats during hypokinesia.

The levels of plasma epinephrine (E) and norepinephrine (NE) were examined in rats exposed to hypokinesia in special adjustable cages for 1, 7 and 75 days. One day before the collection of blood an arterial catheter was inserted into the tail artery and blood samples were collected from undisturbed animals on next day at 8 a.m. and after 1, 6, 12 and 24 hours later. The control groups of animals were kept single in standard animals cages. The content of E, NE and corticosterone was determined in plasma. In rats exposed to hypokinesia for the first time a marked increase of plasma E and NE levels were observed at 1 hour in forced restriction and both E and NE remained elevated after 6, 12 and 24 hours of hypokinesia. A permanent increase of NE and E content in plasma was found in rats exposed to hypokinesia for 7 and 75 days. However, the plasma corticosterone levels were increased only during the first day of hypokinesia, at 7 and 75 days no significant changes in plasma corticosterone were noted. These results showed that there is an important increase of plasma catecholamine levels immediately after the beginning of hypokinesia and the activation of sympathoadrenal system is maintained during the whole period of hypokinesia. No significant changes in adrenocortical system activity were noted during the long-term hypokinesia.