OBJECTIVETo compare the effect of Shen-Fu Injection (SFI) and epinephrine on the expression of sarcoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a) in a pig model with post-resuscitation myocardial dysfunction.

METHODSVentricular fibrillation (VF) was electrically induced in Wu-zhi-shan miniature pigs. After 8 min of untreated VF and 2 min of cardiopulmonary resuscitation (CPR), all animals were randomly administered a bolus injection of saline placebo (SA group, n=10), SFI (0.8 mg/kg, SFI group, n=10) or epinephrine (20 μg/kg, EPI group, n=10). After 4 min of CPR, a 100-J shock was delivered. If the defibrillation attempt failed to attain restoration of spontaneous circulation (ROSC), manual chest compressions were rapidly resumed for a further 2 min followed by a second defibrillation attempt. Hemodynamic variables were recorded, and plasma concentrations of catecholamines were measured. Adenylate cyclase (AC), cyclic adenosine monophosphate (cAMP) and the expressions of β1-adrenoceptor (AR) and SERCA 2a were determined.

RESULTSCardiac output, left ventricular dp/dtmax and negative dp/dtmax were significantly higher in the SFI group than in the SA and EPI groups at 4 and 6 h after ROSC. The expression of β1-AR and SERCA2a at 24 h after ROSC were significantly higher in the SFI group than in the SA and EPI groups (P<0.05 or P<0.01).

CONCLUSIONSThe administration of epinephrine during CPR decreased the expression of SERCA2a and aggravated postresuscitation myocardial function (P<0.01). SFI attenuated post-resuscitation myocardial dysfunction, and the mechanism might be related to the up-regulation of SERCA2a expression.

Adenylyl Cyclases ; metabolism ; Animals ; Blotting, Western ; Cardiac Output ; drug effects ; Cardiopulmonary Resuscitation ; Cyclic AMP ; metabolism ; Dopamine ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; Epinephrine ; blood ; Heart Ventricles ; drug effects ; metabolism ; physiopathology ; Hemodynamics ; drug effects ; Injections ; Male ; Myocardium ; enzymology ; pathology ; Norepinephrine ; blood ; Receptors, Adrenergic, beta-1 ; metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; metabolism ; Swine ; Swine, Miniature ; Up-Regulation ; drug effects

Acetylcholine ; metabolism ; Animals ; Arcuate Nucleus of Hypothalamus ; metabolism ; Dopamine ; metabolism ; Epinephrine ; metabolism ; Female ; Neurotransmitter Agents ; metabolism ; Norepinephrine ; metabolism ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Synaptic Transmission

BACKGROUNDAirway symptoms in asthma are related to decrease of epinephrine secretion, which may be ascribed to elevated nerve growth factor (NGF) in the organism. The aim of this study was to monitor the neuroendocrine alteration in the adrenal medulla of asthmatic rats.

METHODSSixteen rats were randomly divided into two groups (n = 8), control group and asthma group, and the asthmatic rats were sensitized and challenged with ovalbumin (OVA). The levels of NGF, epinephrine and norepinephrine in serum were detected by enzyme linked immunosorbent assay (ELISA), the NGF expression in adrenal medulla was detected by immunohistochemistry, and the changes in the ultrastructure of the adrenal medulla was observed by electron microscopy.

RESULTSThe NGF expression was increased in asthmatic rats compared with control rats. Compared with control rats, the results indicated that the epinephrine level was decreased in asthmatic rats, but no significant difference was found in norepinephrine levels. We found more ganglion cells in the adrenal medulla of asthmatic rats than in control rats, with NGF immunostaining mainly located in these ganglion cells. Electron microscopic images showed the density of chromaffin granula decreased and there was shrunken nucleolemma in the adrenal medullary cells of asthmatic rats.

CONCLUSIONThe innervation of the adrenal medulla is changed in asthmatic rats, and it may contribute to the epinephrine decrease in asthma.

Adrenal Medulla ; metabolism ; ultrastructure ; Animals ; Asthma ; blood ; metabolism ; Bronchoalveolar Lavage ; Enzyme-Linked Immunosorbent Assay ; Epinephrine ; blood ; Male ; Microscopy, Electron, Transmission ; Nerve Growth Factor ; blood ; metabolism ; Norepinephrine ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley

The effects of glucagon and epinephrine on gluconeogenesis in young (4 month) and old (24 month) Fisher 344 rat hepatocytes were compared. In contrast to glucagon, which had a similar effect on gluconeogenesis in both young and old cells, epinephrine caused a smaller increase in gluconeogenesis in old rat hepatocytes than in young hepatocytes. beta2 adrenergic receptor (beta2-AR) expression slightly decreased in aged rat liver, and there were differences between young and old hepatocytes in their patterns of G protein coupled receptor kinases, which are involved in the activation of beta2-AR receptor signal desensitization. The major isoform of the kinase changed from GRK2 to GRK3 and the expression of beta-arrestin, which is recruited by the phosphorylated beta2-AR for internalization and degradation, increased in aged rat liver. GRK3 overexpression also decreased the glucose output from young rat hepatocytes. We conclude that an age-associated reduction in epinephrine-induced gluconeogenesis occurs through the epinephrine receptor desensitizing system.
Adrenergic beta-Agonists/*pharmacology ; Aging/*drug effects ; Animals ; Epinephrine/*pharmacology ; G-Protein-Coupled Receptor Kinase 2/metabolism ; G-Protein-Coupled Receptor Kinase 3/metabolism ; Glucagon/pharmacology ; *Gluconeogenesis/drug effects ; Male ; Models, Biological ; Phosphorylation ; Rats ; Rats, Inbred F344 ; Receptors, Adrenergic, beta-2/agonists/metabolism

The effects of glucagon and epinephrine on gluconeogenesis in young (4 month) and old (24 month) Fisher 344 rat hepatocytes were compared. In contrast to glucagon, which had a similar effect on gluconeogenesis in both young and old cells, epinephrine caused a smaller increase in gluconeogenesis in old rat hepatocytes than in young hepatocytes. beta2 adrenergic receptor (beta2-AR) expression slightly decreased in aged rat liver, and there were differences between young and old hepatocytes in their patterns of G protein coupled receptor kinases, which are involved in the activation of beta2-AR receptor signal desensitization. The major isoform of the kinase changed from GRK2 to GRK3 and the expression of beta-arrestin, which is recruited by the phosphorylated beta2-AR for internalization and degradation, increased in aged rat liver. GRK3 overexpression also decreased the glucose output from young rat hepatocytes. We conclude that an age-associated reduction in epinephrine-induced gluconeogenesis occurs through the epinephrine receptor desensitizing system.
Adrenergic beta-Agonists/*pharmacology ; Aging/*drug effects ; Animals ; Epinephrine/*pharmacology ; G-Protein-Coupled Receptor Kinase 2/metabolism ; G-Protein-Coupled Receptor Kinase 3/metabolism ; Glucagon/pharmacology ; *Gluconeogenesis/drug effects ; Male ; Models, Biological ; Phosphorylation ; Rats ; Rats, Inbred F344 ; Receptors, Adrenergic, beta-2/agonists/metabolism

This study was designed to examine how such factors as hemodialysis parameters, body mass index, renin and aldosterone concentrations, sympathetic nervous activity, and parathyroid hormone concentrations are associated with the control of hypertension in hemodialysis patients. Hemodialysis patients (n=114) were grouped into four categories. Group 1 had normal BP without antihypertensive medication. Group 2 needed one antihypertensive drug, Group 3 needed combination of two or three categories of antihypertensive drugs without minoxidil. Group 4 needed more than three categories of antihypertensive drugs including minoxidil. Parathyroid hormone, beta2-microglobulin, renin and aldosterone, epinephrine, norepinephrine, and hemodialysis parameters were measured. The fractional clearance of urea as Kt/V urea was significantly lower in Group 3 and Group 4 than in Group 2 (p<0.01). Concentrations of parathyroid hormone were significantly higher in Group 4 than the other groups (p<0.01). Pre-hemodialysis norepinephrine concentrations were significantly higher in Group 4 than the other groups (p<0.05). Traditional factors associated with hypertension did not seem to be relevant to the degree of hypertension in hemodialysis patients in the present study. In conclusion, poor Kt/V urea, elevated parathyroid hormone concentrations, and elevated concentrations of plasma norepinephrine seemed to be the factors that might be associated with control of hypertension in hemodialysis patients.
Adult ; Aged ; Aldosterone/*blood ; Analysis of Variance ; Antihypertensive Agents/therapeutic use ; Blood Pressure/drug effects/*physiology ; Epinephrine/blood ; Female ; Humans ; Hypertension/blood/drug therapy/physiopathology ; Kidney Failure, Chronic/blood/physiopathology/therapy ; Male ; Middle Aged ; Norepinephrine/blood ; Parathyroid Hormone/*blood ; *Renal Dialysis ; Renin/*blood ; Sympathetic Nervous System/*physiology ; Urea/metabolism

AIMTo study the protective effect of Polysaccharide of Laminaria L01 on endothelial cell injury inducing by adrenaline.

METHODSIn order to observe the influence of L01 on the release of vWF in endothelial injured rats and HUVEC stimulated by adrenaline, a rat model of endothelial injury was established via injecting adrenaline, the damaged degree of vascular endothelial was evaluated by aortic immunity histochemistry, HUVEC was cultured in vitro, the content of vWF in rat plasma and in supernatant was measured by ELISA.

RESULTSThe measure of intact endodermis lengths (microm) stained by immunohistochemistry demonstrated the length in L01 high-dose group and low-dose group was obviously longer than that of model group (P < 0.05) in the 4th and 5th day during the model made. The content of vWF in rat plasma of L01 high-dose group was lower than that of model group (P < 0.05) in the 4th day, there were significant differences between this two groups, and the content of vWF in rat plasma of both L01 high-dose group and low-dose group was lower than that of model group (P < 0.05) in the 4th and 5th days. In the study of cultured HUVEC, on the 24 h, L01 groups (0.01 mg/ml and 0.1 mg/ml) decreased the supernatant vWF level, and on the 48 h, high-dose group (0.1 mg/ml) also decreased the supernatant vWF level, with significant difference compared with adrenaline group (10 microg/ml, P < 0.05).

CONCLUSIONL01 presented the protective effect on vascular endothelial cell.

Animals ; Endothelial Cells ; drug effects ; Endothelium, Vascular ; cytology ; drug effects ; Epinephrine ; adverse effects ; Female ; Human Umbilical Vein Endothelial Cells ; drug effects ; Humans ; Laminaria ; chemistry ; Male ; Polysaccharides ; pharmacology ; Rats ; Rats, Sprague-Dawley ; von Willebrand Factor ; metabolism

AIMTo elucidate the mechanism of depression induced by chronic unpredictable mild stress (CUMS), the effects of CUMS on serotonin (5-HT), tryptophan, stress hormones and behaviour were investigated in rats.

METHODSDepression was induced by for 8 weeks CUMS and confirmed by behavioral tests, the brain and plasma levels of monoamine neurotransmitters were analyzed by HPLC-ECD techniques, the content of plasma corticosterone was evaluated by I125 cortisol radioactivity immunoassay and the serum tryptophan content was measured by HTTACHI L-8800 amino acid analyzer.

RESULTS(1) Rats exposed to a series of mild, unpredictable stressors for 8 weeks displayed the decreased body weight, reduced scores of open-field test and preference of sucrose solution (P < 0.05). (2) Plasma and brain 5-HT contents in rats after exposure to CUMS 8 weeks decreased significantly (P < 0.05). While serum tryptophan content increased at the same time (P < 0.05). (3) Plasma norepinephrine and epinephrine in rats were increased after CUMS 8 weeks, but there was no difference between control and CUMS group in plasma corticosterone.

CONCLUSIONThe behavioral changes induced by CUMS for 8 weeks are similar to the features of human depression, which may be related to the disturbances of tryptophan metabolism induced by increased norepinephrine and epinephrine in CUMS rat.

Animals ; Depression ; metabolism ; Epinephrine ; metabolism ; Hippocampus ; metabolism ; Male ; Neurosecretory Systems ; metabolism ; Norepinephrine ; metabolism ; Rats ; Rats, Wistar ; Serotonin ; metabolism ; Stress, Psychological ; metabolism

OBJECTIVETo investigate the role of protein kinase C (PKC) in the down-regulation of fibroblast proliferation in normal skin (NFb) and hyperplastic scar (SFb) by adrenaline.

METHODSHuman NFb and SFb cells were cultured in vitro. Phentolamine (in final concentrations of 0 and 3 x 10(-6) micromol/L) was added to the culture medium. One hour later, adrenaline in different final concentrations (0.00, 0.05, 0.10, 0.20 micromol/L) was added to the culture medium and incubated for 24 hours. The cellular proliferation activity and cell viability rate were determined with MTT. The cell culture supernatant was harvested for the determination of LDH activity to assess the toxicity of phentolamine and adrenaline. The phosph-PKC activity was determined with Western-blotting and was semiquantitatively analyzed.

RESULTS(1) After stimulation with adrenaline alone, or combined 0.20 micromol/L adrenaline with 3 x 10(-6) micromol/L phentolamine, the cell viability of both NFb and SFb decreased significantly (P < 0.05 or 0.01). (2) There was no difference in the LDH activity between the cells either stimulated by adrenaline in all concentrations or by combination of adrenaline and phentolamine (P > 0.05). (3) The phosphorylation of PKC in NFb and SFb cells stimulated by 0.05, 0.10, 0.20 micromol/L adrenaline was obviously higher than that before stimulation (P < 0.01). When phentolamine in the concentration of 3 x 10(-6) micromol/L was used alone for stimulation, the phosphorylation of PKC in NFb cells (123 +/- 5) was also evidently higher than that before stimulation (80 +/- 5, P < 0.01). But there was no such effect on SFb cells (P > 0.05). When adrenaline in the concentration of 0.05, 0.10 or 0.20 micromol/L was separately added together with phentolamine in the dose of 3 x 10(6) micromol/L for the stimulation, the phosphorylation of PKC in NFb and SFb cells was evidently lower than that when 3 different concentrations of adrenaline was used alone for stimulation (P < 0.01).

CONCLUSIONAdrenaline can inhibit the proliferation of NFb and SFb by activating PKC through binding alpha adrenaline receptor.

Cell Proliferation ; drug effects ; Cells, Cultured ; Cicatrix, Hypertrophic ; metabolism ; Down-Regulation ; Epinephrine ; adverse effects ; Fibroblasts ; cytology ; Humans ; Phentolamine ; adverse effects ; Phosphorylation ; Protein Kinase C ; metabolism ; Skin ; drug effects

Sleep-disordered breathing (SDB) is associated with increased cardiovascular and cerebrovascular morbidity. Epidemiological and clinic-based studies have shown that SDB is related to impaired glucose tolerance and increased insulin resistance, independent of obesity. Despite of a consistent association between SDB and impaired glucose-insulin metabolism, the mechanism underlying this relationship has not been fully elucidated. It is recognized that hypoxemia and hypercapnia that occur in SDB provoke sympathetic nervous activity and catecholamine, epinephrine and norepinephrine, and cortisol are released. Sympathetic hyperactivity and increased catecholamines can impair glucose homeostasis by increasing glycogenolysis and gluconeogenesis, which can result in increased circulating insulin levels and increased risk of insulin resistance. A prospective study is needed to investigate the causal relationship between SDB and impaired glucose-insulin metabolism in a healthy population without diabetes, hypertension and obesity as etiologic risk factors.
Anoxia ; Catecholamines ; Epinephrine ; Gluconeogenesis ; Glucose ; Glycogenolysis ; Homeostasis ; Hydrocortisone ; Hypercapnia ; Hypertension ; Insulin ; Insulin Resistance ; Metabolism ; Norepinephrine ; Obesity ; Risk Factors ; Sleep Apnea Syndromes* ; Sleep Wake Disorders