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Comparative bioavailability study of two salbutamol tablets in healthy adult volunteers

Chik Z, Basu RC, Pendek R, Lee TC, Mohamed Z

Int J Clin Pharmacol Ther, 2009 Jun;47(6):413-8.
PMID: 19473604

This study was carried out to compare the rate and extent of absorption of a generic salbutamol in oral dosage form (Brethmol, 4 mg) with the proprietary equivalent product (Ventolin, 4 mg), in healthy adult subjects, under fasting conditions. The study was a single dose, randomized, two way crossover study with a four-week washout period. It involved 22 healthy volunteers who received a single dose (4 mg) of the test and the reference products after an overnight fast of at least 10 hours. Blood samples were collected at pre-dose and a serial of 14 samples were collected from each of the subject from 1 h until 48 h post-dose. Plasma concentrations of salbutamol were analyzed using GCMS method. The mean AUC(0-yen) values were 91.26 and 96.45 h.ng/ml for reference and test product, respectively. The mean C(max) values were 12.26 and 12.38 ng/ml and the mean t(max) values were 2.80 and 2.33 hours for reference and test product, respectively. Analysis of variance showed that the 90% confidence intervals on the relative difference of the ratio for the AUC(0-yen) and the C(max) for the test and reference products were contained within the bioequivalence limit (80 - 125%) (C(max): 89.8 - 110.5% and AUC(0-yen): 91.6 - 121.5%). There was no statistically significant difference for the t(max) between the test and reference formulations (p = 0.30). The test formulation was found to be bioequivalent to the reference formulation with regard to AUC(0-yen) and C(max). There was no statistically significant difference in Brethmol and Ventolin t(max). In conclusion, Brethmol and Ventolin are bioequivalent in healthy subjects.

Matched MeSH terms: Adrenergic beta-Agonists/administration & dosage; Adrenergic beta-Agonists/blood; Adrenergic beta-Agonists/pharmacokinetics*
Changing paradigms in the treatment of asthma

Loh LC

Family Physician, 2005;13:5-9.

Significant changes have occurred in relation to how chronic asthma is being treated. Emphasis has now shifted from viewing asthma as a condition of smooth muscle dysfunction to one of chronic inflammation. As such, anti-inflammatory therapy forming the cornerstone of treatment represents the first important milestone in the evolution of asthma treatment. For this purpose, inhaled corticosteroid (ICS) is by far the most effective anti-inflammatory therapy. Another important milestone is the recognition of the superiority of adding long-acting beta2-agonist (LABA) to ICS over escalating ICS dose alone or other forms of add-on therapies in treating asthmatic patients not responding to regular ICS alone. The effectiveness of adding LABA to ICS in treating asthma logically led to combining the two drugs into one single inhaler (salmeterol/fluticasone and budesonide/formoterol) that has the attractiveness of being user-friendly and ensuring that ICS is not missed out. The unique property of formoterol that allows for repetitive flexible dosing paved way to the concept of using Symbicort for both regular maintenance dosing and as required rescue medication. This revolutionary approach has been recently shown to provide improved asthma outcome, achieved at an overall lower or at least comparable corticosteroid intake, and may represent another evolutionary step in the treatment strategy of chronic asthma. Keywords: Asthma treatment, airway inflammation, corticosteroid, long-acting beta2-agonist

Matched MeSH terms: Adrenergic beta-Agonists
Spatial analysis and source profiling of beta-agonists and sulfonamides in Langat River basin, Malaysia

Sakai N, Mohd Yusof R, Sapar M, Yoneda M, Ali Mohd M

Sci Total Environ, 2016 Apr 01;548-549:43-50.
PMID: 26799806 DOI: 10.1016/j.scitotenv.2016.01.040

Beta-agonists and sulfonamides are widely used for treating both humans and livestock for bronchial and cardiac problems, infectious disease and even as growth promoters. There are concerns about their potential environmental impacts, such as producing drug resistance in bacteria. This study focused on their spatial distribution in surface water and the identification of pollution sources in the Langat River basin, which is one of the most urbanized watersheds in Malaysia. Fourteen beta-agonists and 12 sulfonamides were quantitatively analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A geographic information system (GIS) was used to visualize catchment areas of the sampling points, and source profiling was conducted to identify the pollution sources based on a correlation between a daily pollutant load of the detected contaminant and an estimated density of human or livestock population in the catchment areas. As a result, 6 compounds (salbutamol, sulfadiazine, sulfapyridine, sulfamethazine, sulfadimethoxine and sulfamethoxazole) were widely detected in mid catchment areas towards estuary. The source profiling indicated that the pollution sources of salbutamol and sulfamethoxazole were from sewage, while sulfadiazine was from effluents of cattle, goat and sheep farms. Thus, this combination method of quantitative and spatial analysis clarified the spatial distribution of these drugs and assisted for identifying the pollution sources.

Matched MeSH terms: Adrenergic beta-Agonists/analysis*
Selective extraction of salbutamol from human plasma with the use of phenylboronic acid

Koh YM, Saleh MI, Tan SC

J Chromatogr A, 2003 Feb 14;987(1-2):257-67.
PMID: 12613820

An investigation was conducted on the usage of a single-step extraction procedure involving the retention of a phenylboronate-salbutamol complex on an end-capped C18 solid-phase sorbent to determine the level of salbutamol in human plasma samples. Propranolol, a beta-blocker, was chosen as the internal standard for this assay. In this solid-phase clean-up method, 50 mM sodium carbonate buffer, pH 9.60, was used for conditioning the column as well as washing the endogenous interference. Under the optimal conditions, the recovery of salbutamol from spiked plasma samples was found to be high and reproducible with mean recoveries (n = 3) of more than 90% after elution by using 50% 1 M trifluoroacetic acid in methanol. This sample clean-up step was effectively analyzed under reversed-phase high-performance liquid chromatography with fluorimetric detection. The method was successfully applied to the routine measurement of salbutamol in human plasma from the bioequivalence study on the different administration route of salbutamol. Quantification of salbutamol was convincingly reported with the correlation of coefficient of 0.9980 for the concentration range from 0 to 1000 ng ml(-1). An adequate precision was achieved with both between- and within-day precisions of less than 10% (n = 6) for 100 and 1000 ng ml(-1) and less than 15% (n = 6) for 10 ng ml(-1).

Matched MeSH terms: Adrenergic beta-Agonists/blood*
Fulltext Prescription of oral short-acting beta 2-agonist for asthma in non-resource poor settings: A national study in Malaysia

Chin MC, Sivasampu S, Khoo EM

PLoS One, 2017;12(6):e0180443.
PMID: 28662193 DOI: 10.1371/journal.pone.0180443

OBJECTIVE: Use of oral short-acting beta 2-agonist (SABA) persists in non-resource poor countries despite concerns for its lower efficacy and safety. Utilisation and reasons for such use is needed to support the effort to discourage the use of oral SABA in asthma. This study examined the frequency of oral short-acting Beta 2-agonist (SABA) usage in the management of asthma in primary care and determined correlates of its usage.
METHODS: Data used were from the 2014 National Medical Care Survey in Malaysia, a nationally representative survey of primary care encounters (weighted n = 325818). Using methods of analysis of data for complex surveys, we determined the frequency of asthma diagnosis in primary care and the rate of asthma medication prescription, which includes oral SABA. Multivariate logistic regression models were built to assess associations with the prescription of oral SABA.
RESULTS: A weighted estimate of 9241 encounters presented to primary care with asthma in 2014. The mean age of the patients was 39.1 years. The rate of oral SABA, oral steroids, inhaled SABA and inhaled corticosteroids prescriptions were 33, 33, 50 and 23 per 100 asthma encounters, respectively. It was most commonly used in patients with the age ranged between 20 to less than 40 years. Logistic regression models showed that there was a higher odds of oral SABA usage in the presence of respiratory infection, prescription of oral corticosteroids and in the private sector.
CONCLUSION: Oral SABA use in asthma is found to be common in a non- resource poor setting and its use could be attributed to a preference for oral medicines along undesirable clinical practices within a fragmented health system.

Matched MeSH terms: Adrenergic beta-Agonists/administration & dosage; Adrenergic beta-Agonists/therapeutic use*
Validation of ELISA test kits for detection of beta-agonist residues in meat

Ponniah J, Muhammad K, Abdullah S, Ganapathy KK, bt Sheikh Abdul Hamid N

Southeast Asian J Trop Med Public Health, 2004 Jun;35(2):481-7.
PMID: 15691160

Three ELISA test kits, the Randox ELISA beta-agonist test kit, Euro-Diagnostica test kit, and Ridascreen beta-agonist test kit, were evaluated for screening of meat and liver for beta-agonist residues in fortified and field-incurred samples. It was found that the Randox beta-agonist test kit was more suitable as a screening tool due to its accuracy, ease of use, and lower cost. The tests were able to detect beta-agonist residues at the minimum level of detection, as claimed by the suppliers. The performance of the method as assessed through recovery rates of beta-agonists in fortified samples was satisfactory with a low coefficient of variation (1-3%). Repeatability, as measured through the coefficient of correlation was also satisfactory. For field-incurred positive samples, the test kit showed a sensitivity of 100% and a low rate of false positives for goat and cow tissues. However, a high rate of apparent false positives was obtained for tissues of swine.

Matched MeSH terms: Adrenergic beta-Agonists/analysis*; Adrenergic beta-Agonists/poisoning
Bronchodilator response to inhaled beta-2 agonist and anticholinergic drugs in patients with bronchiectasis

Hassan JA, Saadiah S, Roslan H, Zainudin BM

Respirology, 1999 Dec;4(4):423-6.
PMID: 10612580 DOI: 10.1046/j.1440-1843.1999.00215.x

OBJECTIVE: An increase in incidence of reversible airflow obstruction and bronchial hyperresponsiveness occurs in patients with bronchiectasis. We conducted a study to assess the efficacy of bronchodilators in the treatment of bronchiectasis.
METHODOLOGY: Twenty-four patients with confirmed bronchiectasis were studied. Each patient inhaled fenoterol 400 microg administered by metered dose inhaler via a spacer after a baseline lung function and a lung function test was repeated 30 min later. This was followed by a second dose of fenoterol 5 mg via nebulizer and another lung function test 30 min later. A repeat study was done at least 24 h later with ipratropium bromide 40 microg by metered dose inhaler and 500 microg by a nebulizer.
RESULTS: The results showed a significant improvement from baselines (mean percentage change +/- SD) of peak expiratory flow rate (PEF) by 8.5 +/- 8.72% and 15.3 +/- 11.63%, forced expiratory volume in 1 s (FEV1) by 8.77 +/- 9.69% and 10.2 +/- 12.2% and forced vital capacity (FVC) by 10.25 +/- 11.61% and 10.09 +/- 10.88% after low- and high-dose fenoterol, respectively. The improvements after low- and high-dose ipratropium bromide for PEE FEV1 and FVC were 9.89 +/- 9.35% and 14.39 +/- 12.82%, 9.38 +/- 10.41% and 13.52 +/- 17.09%, and 8.03 +/- 10.85% and 9.63 +/- 13.85%, respectively. Eleven patients (45.8%) responded to one or both bronchodilators significantly (> 15% improvement in FEV1). Five patients (20%) responded to both, three (12%) to fenoterol alone and another three (12%) to ipratropium bromide alone.
CONCLUSION: There is significant bronchodilator response in a subset of patients with bronchiectasis and patients with bronchiectasis should therefore undergo bronchodilator testing. Skin prick testing against a panel of nine allergens done on each individual yielded a positive result in 13 patients (54.2%).

Matched MeSH terms: Adrenergic beta-Agonists/administration & dosage*
Beta-agonist residues in cattle, chicken and swine livers at the wet market and the environmental impacts of wastewater from livestock farms in Selangor State, Malaysia

Sakai N, Sakai M, Mohamad Haron DE, Yoneda M, Ali Mohd M

Chemosphere, 2016 Dec;165:183-190.
PMID: 27654221 DOI: 10.1016/j.chemosphere.2016.09.022

Fourteen beta-agonists were quantitatively analyzed in cattle, chicken and swine liver specimens purchased at 14 wet markets in Selangor State, Malaysia, by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The health risks of ractopamine and clenbuterol residues in the Malaysian population were assessed based on quantitative data and meat consumption statistics in Malaysia. Wastewater samples collected at swine farms (n = 2) and cattle/cow farms (n = 2) in the Kuala Langat district were analyzed for the presence for the 14 compounds. Wastewater in chicken farms was not collected because there was negligible discharge during the breeding period. The environmental impacts caused by beta-agonists discharged from livestock farms were spatially assessed in the Langat River basin using a geographic information system (GIS). As a result, 10 compounds were detected in the liver specimens. Ractopamine, which is a permitted compound for swine in Malaysia, was frequently detected in swine livers; also, 9 other compounds that are prohibited compounds could be illegally abused among livestock farms. The health risks of ractopamine and clenbuterol were assessed to be minimal as their hazard quotients were no more than 7.82 × 10(-4) and 2.71 × 10(-3), respectively. Five beta-agonists were detected in the wastewater samples, and ractopamine in the swine farm resulted in the highest contamination (30.1 μg/L). The environmental impacts of the beta-agonists in the Langat River basin were generally concluded to be minimal, but the ractopamine contamination released from swine farms was localized in coastal areas near the estuary of the Langat River basin because most swine farms were located in that region.

Matched MeSH terms: Adrenergic beta-Agonists/analysis*
Disability and breathlessness in asthmatic patients--a scoring method by repetitive inspiratory effort

Loh LC, Puah SH, Ho CV, Chow CY, Chua CY, Jayaram J, et al.

J Asthma, 2005 Dec;42(10):853-8.
PMID: 16393724

Measurement of disability and breathlessness in asthma is important to guide treatment. Using an incentive spirometer, Triflo II (Tyco Healthcare, Mansfield, MA, USA), we developed a three-minute respiratory exercise test (3-MRET) to score the maximal breathing capacity (MBC) and perception of dyspnea (POD) index by means of repetitive inspiratory efforts achieved within 3 minutes. POD index was calculated based on the ratio of breathlessness on visual analogue scale over MBC score. In 175 normal healthy subjects and 158 asthmatic patients of mild (n = 26), moderate (n = 78), and severe (n = 54), severity, the mean (95% CI) MBC scores in mild, moderate, and severe asthma patients were 168 (145-192), 153 (136-169), and 125 (109-142) respectively, and 202 (191-214) in normal subjects (p < 0.001). The mean POD index in mild, moderate, and severe asthma patients was 16 (9-23), 25 (14-37), and 57 (14-100), respectively, and 6 (4-7) in normal subjects (p < 0.001). Intraclass correlation coefficients for MBC score and POD index in 17 asthmatic and 20 normal subjects were high. In 14 asthmatic patients randomized to receiving nebulized beta2-agonist or saline in a cross-over, double-blind study, % forced expiratory volume in one second (FEV1) change correlated with % change in MBC score [r(s) = 0.49, p < 0.01] and POD index [r(s)-0.46, p = 0.012]. In 21 asthmatic and 26 normal subjects, the MBC score and POD index correlated with the walking distance and walking POD index of the six-minute walking test (6MWT). We conclude that 3MRET is discriminative between asthmatic patients of varying severity and normal subjects, is reproducible, is responsive to bronchodilator effect, and is comparable with 6MWT. Taken together, it has the potential to score disability and POD in asthma simply and effectively.

Matched MeSH terms: Adrenergic beta-Agonists/therapeutic use
Fulltext Alpha1B-adrenoceptors mediate adrenergically-induced renal vasoconstrictions in rats with renal impairment

Khan MA, Sattar MA, Abdullah NA, Johns EJ

Acta Pharmacol Sin, 2008 Feb;29(2):193-203.
PMID: 18215348 DOI: 10.1111/j.1745-7254.2008.00727.x

This study examined whether alpha1B-adrenoceptors are involved in mediating adrenergically-induced renal vasoconstrictor responses in rats with pathophysiological and normal physiological states.

Matched MeSH terms: Adrenergic beta-Agonists/pharmacology
Fulltext Beta Adrenergic Receptors Stimulation Attenuates Phosphorylation of NF-κB and IκBα in Hyperglycemic Endothelial Cells

Safi SZ, Shah H, Qvist R, Bindal P, Mansor M, Yan GOS, et al.

Cell Physiol Biochem, 2018;51(3):1429-1436.
PMID: 30485834 DOI: 10.1159/000495591

BACKGROUND/AIMS: NF-κB induces transcription of a number of genes, associated with inflammation and apoptosis. In this study, we have investigated the effect of β-adrenergic receptor stimulation on NF-κB and IκBα in HUVECs.
METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured in high and low glucose concentrations. All HUVECs were treated with different concentrations of isoproterenol and propranolol for different time periods. The analytical procedures consisted of Western Blot, ELISA, DCFH-DA and TUNEL assays.
RESULTS: Isoproterenol (agonist of a beta-adrenergic receptor) significantly reduced phosphorylation at Ser-536 of NF-κB; and Ser-32 and Ser-36 of IκBα in hyperglycemic HUVECs. Isoproterenol also significantly reduced apoptosis and ROS generation. No effect of IκBα was observed on Tyr-42 phosphorylation. The effect of isoproterenol was reversed by the antagonist propranolol. We also checked if NF-κB inhibitor MG132 causes any change at the level of apoptosis. However, we observed an almost similar effect.
CONCLUSION: Given data demonstrates that beta-adrenergic receptors stimulation has a protective effect on HUVECs that might be occuring via NF-κβ and IκBα pathway.

Matched MeSH terms: Adrenergic beta-Agonists/pharmacology*
Fulltext Co-administration of conjugated linoleic acid and rosiglitazone increases atherogenic co-efficient and alters isoprenaline-induced vasodilatation in rats fed high fat diet

Chai BK, Lau YS, Loong BJ, Rais MM, Ting KN, Dharmani DM, et al.

Physiol Res, 2018 Nov 14;67(5):729-740.
PMID: 29750886

The cis(c)-9, trans(t)-11 (c9,t11) and t10,c12 isomers of conjugated linoleic acid (CLA) have been reported as agonists of peroxisome proliferator-activated receptor (PPAR) and beneficial in lipidemia and glycemia. However, it is unclear whether CLA isomers enhance or antagonize effects of conventional drugs targeting PPAR. Male Sprague-Dawley rats were fed high fat diet (HFD) for 8 weeks and treated without or with CLA, rosiglitazone or both for 4 weeks. Oral glucose tolerance and surrogate markers of insulin resistance were not significantly different for all treatments compared to untreated normal diet (ND) or HFD group, except lipoprotein levels. The combination of CLA and rosiglitazone had suppressed levels of low and high density lipoproteins (46 % and 25 %, respectively), compared to HFD-alone. Conversely, the atherogenic co-efficient of the animals received HFD or HFD+rosiglitazone+CLA was 2-folds higher than ND, HFD+rosiglitazone or HFD+CLA. Isolated aortic rings from the combined CLA and rosiglitazone treated animals were less sensitive to isoprenaline-induced relaxation among endothelium-denuded aortas with a decreased efficacy and potency (R(max)=53+/-4.7 %; pEC50=6+/-0.2) compared to endothelium-intact aortas (R(max)=100+/-9.9 %; pEC50=7+/-0.2). Our findings illustrate that the combination of CLA and rosiglitazone precede the atherogenic state with impaired endothelium-independent vasodilatation before the onset of HFD-induced insulin resistance.

Matched MeSH terms: Adrenergic beta-Agonists/pharmacology
Mechanisms of β-adrenergic receptors agonists in mediating pro and anti-apoptotic pathways in hyperglycemic Müller cells

Safi SZ, Saeed L, Shah H, Latif Z, Ali A, Imran M, et al.

Mol Biol Rep, 2022 Oct;49(10):9473-9480.
PMID: 35925485 DOI: 10.1007/s11033-022-07816-0

BACKGROUND: The current study aimed to investigate the stimulatory effect of beta-adrenergic receptors (β-ARs) on brain derived neurotropic factor (BDNF) and cAMP response element binding protein (CREB).
METHODS: Human Müller cells were cultured in low and high glucose conditions. Cells were treated with xamoterol (selective agonist for β1-AR), salmeterol (selective agonist for β2-AR), isoproterenol (β-ARs agonist) and propranolol (β-ARs antagonist), at 20 µM concentration for 24 h. Western Blotting assay was performed for the gene expression analysis. DNA damage was evaluated by TUNEL assay. DCFH-DA assay was used to check the level of reactive oxygen species (ROS). Cytochrome C release was measured by ELISA.
RESULTS: Xamoterol, salmeterol and isoproterenol showed no effect on Caspase-8 but it reduced the apoptosis and increased the expression of BDNF in Müller cells. A significant change in the expression of caspase-3 was observed in cells treated with xamoterol and salmeterol as compared to isoproterenol. Xamoterol, salmeterol and isoproterenol significantly decreased the reactive oxygen species (ROS) when treated for 24 hours. Glucose-induced cytochrome c release was disrupted in Müller cells.
CONCLUSION: β-ARs, stimulated by agonist play a protective role in hyperglycemic Müller cells, with the suppression of glucose-induced caspase-3 and cytochrome c release. B-Ars may directly mediate the gene expression of BDNF.

Matched MeSH terms: Adrenergic beta-Agonists/pharmacology
Chronic treatment with losartan and carvedilol differentially modulates renal vascular responses to sympathomimetics compared to treatment with individual agents in normal Wistar Kyoto and spontaneously hypertensive rats

Abdulla MH, Sattar MA, Abdullah NA, Khan MA, Abdallah HH, Johns EJ

Eur J Pharmacol, 2009 Jun 10;612(1-3):69-74.
PMID: 19356722 DOI: 10.1016/j.ejphar.2009.03.064

This study set out to investigate the impact of chronic cumulative blockade of angiotensin II and adrenoceptors in WKY and SHR and to explore how the renovascular responses to adrenergic and angiotensin II receptor agonists may be interdependent. Rats were treated with either losartan, carvedilol or losartan+carvedilol for 7 days and on day eight, animals were pentobarbitone anaesthetized and prepared for renal haemodynamic study. Dose-response relationships were determined in terms of reduction/elevation in the magnitude of renal blood flow in response to intrarenal arterial injection of dopamine, phenylephrine and isoprenaline. Renal vascular responses were blunted in WKY and SHR treated with either losartan or carvedilol as compared to their untreated counterparts (P<0.05). In the combined treated rats, the vascular responses to isoprenaline and phenylephrine were restored to levels observed in the untreated rats, but the renal vasoconstrictor responses to dopamine decreased (P<0.05) in both WKY and SHR. There was a reduction of (P<0.05) in the magnitude of the isoprenaline induced renal vasodilation in all SHR as compared to WKY groups. The data obtained showed that the renal vascular action of dopamine, phenylephrine and isoprenaline depended on an intact renin-angiotensin system (RAS) in WKY and SHR. Treatment with losartan or carvedilol blunted the renal vasoconstrictor/vasodilator responses to sympathomimetics which was attenuated with the combined treatment. These observations using chronic blockade of adrenergic and angiotensin receptors demonstrated that there was a long standing interdependency between the RAS and sympathetic nervous system (SNS) in determining the responsiveness of the renal vasculature of normal and hypertensive rats.

Matched MeSH terms: Adrenergic beta-Agonists/pharmacology
Fulltext Glucose uptake and lipid metabolism are impaired in epicardial adipose tissue from heart failure patients with or without diabetes

Burgeiro A, Fuhrmann A, Cherian S, Espinoza D, Jarak I, Carvalho RA, et al.

Am J Physiol Endocrinol Metab, 2016 Apr 01;310(7):E550-64.
PMID: 26814014 DOI: 10.1152/ajpendo.00384.2015

Type 2 diabetes mellitus is a complex metabolic disease, and cardiovascular disease is a leading complication of diabetes. Epicardial adipose tissue surrounding the heart displays biochemical, thermogenic, and cardioprotective properties. However, the metabolic cross-talk between epicardial fat and the myocardium is largely unknown. This study sought to understand epicardial adipose tissue metabolism from heart failure patients with or without diabetes. We aimed to unravel possible differences in glucose and lipid metabolism between human epicardial and subcutaneous adipocytes and elucidate the potential underlying mechanisms involved in heart failure. Insulin-stimulated [(14)C]glucose uptake and isoproterenol-stimulated lipolysis were measured in isolated epicardial and subcutaneous adipocytes. The expression of genes involved in glucose and lipid metabolism was analyzed by reverse transcription-polymerase chain reaction in adipocytes. In addition, epicardial and subcutaneous fatty acid composition was analyzed by high-resolution proton nuclear magnetic resonance spectroscopy. The difference between basal and insulin conditions in glucose uptake was significantly decreased (P= 0.006) in epicardial compared with subcutaneous adipocytes. Moreover, a significant (P< 0.001) decrease in the isoproterenol-stimulated lipolysis was also observed when the two fat depots were compared, and it was strongly correlated with lipolysis, lipid storage, and inflammation-related gene expression. Moreover, the fatty acid composition of these tissues was significantly altered by diabetes. These results emphasize potential metabolic differences between both fat depots in the presence of heart failure and highlight epicardial fat as a possible therapeutic target in situ in the cardiac microenvironment.

Matched MeSH terms: Adrenergic beta-Agonists/pharmacology

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