以“肾上腺素受体激动药”为例探索“基因式”课程思政的教学路径

在深入推进校园课程思政建设的时代背景下,文章探讨了医药学专业基础课程——药理学教学中思政教育的有机融入路径。以“肾上腺素受体激动药”的教学为例,文章从师资建设、思政元素的深入挖掘(识别思政教育的遗传密码)、构建思政素材库(积累丰富的思政教育氨基酸)以及精细的教学设计(确保思政教育的蛋白质得以准确表达)等方面,详细阐述了思政教育如何以“基因式”的方式融入药理学教学的具体路径,依据本章的专业教学内容,制定了明确的思政目标,深入挖掘了与之相关的思政元素,并运用多种载体形式的素材,巧妙地在不同教学环节中融入思政教育;将思政教育延伸至课后、线上教学和实验教学,实现了广泛而深入的教育效果,获得了学生的认可。

米拉贝隆联合索利那新防治前列腺电切术后导尿管相关膀胱刺激症的疗效分析

目的论证米拉贝隆联合索利那新防治经尿道前列腺电切术(TURP)术后导尿管相关膀胱刺激症(CRBD)的有效性和安全性。方法将符合标准的108例接受TURP手术的前列腺增生患者随机分为三组,每组36例;术前1天开始M+S组给予口服米拉贝隆50 mg/d联合索利那新5 mg/d;S组服用单药索利那新5 mg/d;C组仅接受TURP手术。对术后出现中度以上CRBD的患者进行自制综合量表评分,达到设定标准的予静脉滴注间苯三酚处理。观察各组术后第1、3、5天CRBD发生情况,术后5天内静脉给药量,持续膀胱冲洗时间及药物不良反应。结果共有106例患者纳入最终的分析,M+S组除了术后第1天在中度和重度CRBD的发生率上与S组相当外,在其他时间节点的CRBD总发生率、中度和重度CRBD发生率及静脉给药量上均明显优于S组及C组(P<0.05);S组与C组相比在任何时间节点均没有降低CRBD总发生率(P>0.05),但在中度和重度CRBD的发生率及静脉用药量上优于C组(P<0.05)。3组术前及术后第1、3、5天的心率、收缩压、舒张压值均无统计学意义(P>0.05);M+S组和S组中新发口干、便秘的例数略多于C组,但是差异无统计学意义(P>0.05);M+S组额外报告1例新发皮疹。结论米拉贝隆联合索利那新可降低TURP术后CRBD的发生率,减少患者静脉解痉药物的应用,较单药索利那新效果更优且不增加药物不良反应。

Mechanism of Anti-β-adrenoceptor Antibody Mediated Myocardial Damage in Dilated Cardiomyopathy

Antibodies against &-adrenoceptor can be detected in serum of patients with dilated cardiomyopathy (DCM), which have 5-agonist-like activity, and induce a positive chronotropic effect on cardiac myocytes by its persistence at full strength. Effects of the antibodies against Padrenoceptor from sera of patients with DCM on myocardial cytotoxicity and cytoplasmic free Ca2+-concentration (LCa2+ji) were observed in the cultured single layer SD rat ventricular cells by using the cytotoxicity assay and fluorescent Ca2+- indicat0r fura-2/AM. The positive sera of the anti-&adrenoceptor antibodies from patients with DCM markedly enhanced myocardial [Ca2+]i. Betaloc, a 5, -receptor blocker, might inhibit the increase of the antibody-mediated myocardial [Ca2+]i, and the sera from healthy donors had no effect on myocardial [Ca2+]i,. Our results suggest that the anti-β-adrenoceptor antibody might increase myocardial [Ca2+]i, and result in myocardial damage. The antibodies might activate receptor-gating Ca2+-channel, thereby causing myocardial [Ca2+]i, rise and calcium overload. Early use of betaloc is recommended in the treatment of dilated cardiomyopathy.

β_2-adrenoceptor in obstructive airway diseases:Agonism, antagonism or both?

Obstructive airway disease is a complex disease entity including several maladies characterized by bronchoconstriction and abnormal airway inflammation. Reversing bronchoconstriction leads to symptomatic relief and improvement in quality of life, both in reversible(bronchial asthma) and partially reversible(chronic obstructive airway disease) obstructive airway diseases. β2-adrenoceptor expressed in human airway is the main β-receptor subtype, and its activation in airway smooth muscle cells leads to bronchodilatation. Drugs targeting β-adrenoceptors have been around for many years, for which agonists of the receptors are used in bronchodilation while antagonists are used in cardiovascular diseases. This review article summarizes the effect and usage of β2-agonist in obstructive airway disease, addressing the benefits and potential risks of β2-agonist. The article also looks at the safety of β-blocker usage for cardiovascular disease in patients with obstructive airway disease. There is also emerging evidence that non-selective β-blockers with inverse agonism ironically can have longterm beneficial effects in obstructive airway disease that is beyond cardiovascular protection. Further trials are urgently needed in this area as it might lead to a dramatic turnaround in clinical practice for obstructive airway diseases as has already been seen in the usage of β-blockers for heart failure.

Regulation ofβ2-adrenoceptors in brain glia:implications for neuroinflammatory and degenerative disorders

Noradrenaline:Within the central nervous system(CNS),the primary source of the catecholamine neurotransmitter noradrenaline is the locus coeruleus(LC)in the pontine tegmentum,with LC neurons projecting to almost all regions of the brain and spinal cord.Following its release from LC neurons,noradrenaline has wide ranging effects.For example,noradrenaline is the endogenous agonist for G-coupledα-andβ-adrenoceptors that are expressed on many cell types,including neurons and glia,in both the peripheral nervous system and CNS.It is via these receptors that noradrenaline exerts its anti-inflammatory and neurotrophic effects in the brain.Noradrenaline additionally has adrenoceptor-independent neuroprotective actions,and as such plays a role in free radical scavenging and reducing oxidative stress(Feinstein et al.,2016).

Differential Expression of Alpha-Adrenoceptor Subtypes in Rat Dorsal Root Ganglion after Chronic Constriction Injury

Summary： mRNAs of alpha-adrenoceptor （α-AR） subtypes are found in neurons in dorsal root ganglion （DRG） and change after peripheral nerve injury. In this study, the distribution of α-AR subtype proteins was studied in L5 DRG of normal rats and rats with chronic constriction injury of sciatic nerve （CCI）. Using immunofluorescence technique, it was found that α1A-, α1B-, and α2A-AR proteins were expressed in large, medium, and small size neurons in normal DRG, and significantly increased in all size neurons 14 days after CCI. α1D- and α2C-AR was also expressed in all size neurons in normal DRG. However, α1D-AR was significantly increased and α2C-AR was decreased in small size neurons 14 days post CCI. α2B-AR neurons were not detectable in normal and CCI DRG. Co-expression of α1A- and α2A-AR in the same neuron was observed in normal DRG and increased post CCI. Collectively, these results indicated that there is distinct distribution of α-AR subtypes in DRG neurons, and the distribution and levels of expression of α-AR subtypes change differently after CCI. The up-regulation of α-AR subtypes in DRG neurons may play an important role in the process of generating and transmitting neuropathic pain.

Neuronal changes resulting in up-regulation of alpha-1 adrenoceptors after peripheral nerve injury

Under normal conditions, the sympathetic neurotransmitter noradrenaline inhibits the production and release of pro-inflammatory cytokines. However, after peripheral nerve and tissue injury, pro-inflammatory cytokines appear to induce the expression of the alphalA-adreno- ceptor subtype on immune cells and perhaps also on other cells in the injured tissue. In turn, noradrenaline may act on up-regulated alphal-adrenoceptors to increase the production of the pro-inflammatory cytokine interleukin-6. In addition, the release of inflammatory mediators and nerve growth factor from keratinocytes and other cells may augment the expression of alphal-adrenoceptors on peripheral nerve fibers. Consequently, nociceptive afferents acquire an abnormal excitability to adrenergic agents, and inflammatory processes build. These mechanisms could contribute to the development of sympathetically maintained pain in conditions such as post-herpetic neuralgia, cutaneous neuromas, amputation stump pain and complex regional pain syndrome.

Primary study on correlation betweenβ_2-adrenoceptor haplotypes and asthma in children of Han nationality in Chongqing

Objective:To investigatethecorrelationbetweenβ 2 -adrenergicreceptors(β 2 -AR)haplotypesandasthmaof Hannationalitychildrenin Chongqingregion.Methods:PCRandrestrictionfragmentanalysiswereusedto study16,27lociof theβ 2 -ARpolymorphismin76unrelatedasthmaticchildrenandin100healthychildrenandadultsof Hannationali-ty as control.A statisticalanalysisof thecorrelationbetweenglycine(Gly)16allele,Gly16/glutamine(Gln)27haplotype andasthmaticclinicalstatuswas carriedout.Results:Therewas no significantincreaseof thefrequencyof Gly16and Gln27alleleintheasthmaticgroupas comparedwiththecontrolgroup(P>0.05).Therewasa significantincreaseof the frequencyof Gly16alleleandGly16/Gln27haplotypein severeasthmaticcasesthanin themildandmoderateasthmatic ones(P<0.01,0.05).Conclusion:Itis consideredthatasthmais notcausedby GlyandGlnallelesofβ 2 -ARpolymor-phisms.Gly16alleleandGly16/Gln27haplotypearepossiblycorrelatedwiththeseverityof theclinicalmanifestationsin thechildrenof HannationalityinChongqing.

Reducing sympathetic nervous tone in aged rats bettered cardiomyocyte contraction by improving the response of β_2-adrenoceptor

The study was to investigate the effect of reducing central sympathetic nervous tone with clonidine on cardiomyocyte contraction,and further to analyze the influence of reducing the central sympathetic nervous tone on response of β1 and β2-AR in aged ventricular myocytes.Sprague-Dawley rats were randomly divided into three groups:adult group,aged group and aged group with clonidine.

Effect of β blockers on β_3-adrenoceptor mRNA Expression in the Rats with Chronic Heart Failure

Objectives To investigate the changes of β3-adrenoceptor (β3-AR) mRNA expression in the rats with chronic heart failure (CHF), and to explore the effect of β blockers (βBs) on β3 mRNA expression. Methods Thirty-four rats were randomly divided into Sham group (n = 10) and heart failure group (n = 24). Rat model was established by aortic constriction. The survival rats in heart failure group were divided into heart failure control group (HF group, n = 6), metoprolol group (MET group, n = 8) and carvedilol group (CAR group, n = 8) three months after operation. Metoprolol tartarte was started orally with 12 mg·kg-1·d-1, carvedilol with 6 mg·kg-1·d-1, isometric saline was started in HF group. After three months of drug therapy, measurement of hemodynamics, index of ventricular mass, the level of β3-AR mRNA expression were performed. Results Compared with Sham group, left ventricular end systolic pressure (LVESP), and the absolute values of maximal rate of rise and fall ( ± dp/dtmax) of left ventricular pressure were all significantly decreased (P < 0.01), left ventricular end diastolic pressure (LVEDP) was significantly increased in HF group (P < 0.01). The hemodynamic parameters were improved by βBs, and carvedilol was more effective than metoprolol (P < 0.01). The index of ventricular mass was higher in HF group than MET group, CAR group and Sham group (P < 0.01). βBs significantly decreased the index of left ventricular mass (LVMI), and Carvedilol was more effective than metoprolol (P < 0.01). The index of right ventricular mass (RVMI) did not change in MET group (P > 0.05), but significant decrease could be seen in CAR group (P < 0.01). The level of β3-AR expression in left ventricle was greater than that in right ventricle whether in the failing heart or in the non-failing heart. Compared with Sham group, the level of β3-AR mRNA expression was significantly increased in HF group (P < 0.01). The levels of β3-AR mRNA expression showed a remarkable decrease in CAR group(P < 0.01), but was not seen in MET group. Conclusions The β3-AR expression level remarkably increases in the rat’s left and right failing ventricles. Carvedilol is more effective on improving hemodynamics and attenuating ventricular remodeling than metoprolol in the rats with CHF. Carvedilol rather than metoprolol downregulates β3-AR expression in the rat’s failing ventricles. The beneficial effect of carvedilol in CHF maybe partly due to the downregulation of β3-AR expression in the failing heart.

Design and Synthesis of Novel Aryloxyalkyl-arylpiperazine Derivatives as α_(1A)-Adrenoceptor Antagonists

A series of 1-[2-(substituted phenoxy)ethyl]-4-(2-methoxyphenyl)-piperazine deriva- tives have been synthesized. The radioligand receptor binding assay indicated that most of them bind with α1-adrenoceptor specifically, and one of the compound possessed subtype A selectivity.

Co-Localization of Alpha1-Adrenoceptors and GPR55: A Novel Prostate Cancer Paradigm?

α1-adrenoceptors (α1-ARs) and “cannabinoid-like” G Protein Coupled Receptor 55 (GPR55) belong to the G-protein coupled receptor (GPCR) family and play a crucial role in regulating prostate function. Although physical and functional interactions between the cannabinoid and adrenergic systems have been reported, analysis of functional interactions between α1-AR and GPR55 in normal and neoplastic prostate has not been reported. Since GPR55 levels are high in rodent adrenal gland, we propose a function link between the adrenergic system and GPR55 receptor. Confocal Laser Scanning Microscopy (CLSM) was employed to examine the endogenous α1-AR and GPR55 expression and their co-localization, expressed as fluorescence, in vitro in human andro-gen-insensitive PC-3 and androgen-sensitive LNCaP prostatic carcinoma cell lines, using the fluo-rescent ligands—Syto 62 (nuclear stain), BODIPY FL-Prazosin (QAPB;fluorescent quinazoline α1-AR ligand) and Tocriflour (T1117;a novel fluorescent diarylpyrazole cannabinoid/GPR55 ligand). Fluorescent ligand binding in untreated PC-3 cells and LNCaP cells and spheroids showed hetero-geneous expression of both α1-ARs and GPR55. A small proportion of cells had both α1-ARs and GPR55 in relatively equal numbers indicating a degree of co-localization. Co-localization of fluo-rescent ligand binding exhibited a stronger correlation in LNCaP (0.87) as compared to PC-3 (0.63) cells. Upregulation of α1-AR was observed in PC-3 cells following chronic doxazosin incubation. Robust T1117 binding, suggestive of GPR55 upregulation, was also observed in these cells. The presence of subtype-rich cells with a degree of co-localization between α1-ARs and GPR55 indicates a possibility for dimerisation or functional interaction and a new paradigm for functional synergism in which interactions may be either between cells or involve converging intracellular signaling processes.

Selective changes in the <i>α</i>-adrenoceptor-mediated contraction in the senescent rat urinary bladder

The urinary bladder is innervated and functionally regulated by the autonomic nervous system. In order to elucidate the mechanism of functional changes in aged rat urinary bladder, we studied the influence of senescence on, 1) the α-adrenergic contractile response to phenylephrine in the urinary bladder body and trigone, 2) the muscarinic contractile response to carbachol in the body and trigone. The binding characteristics of [3H]quinuclidinyl benzilate (QNB) to muscarinic cholinoceptors were compared in young and aged bladder. Bladders from young (2 - 3 month-old) and aged (27 month-old) male Fischer 344 rats were isolated, cut into strips and mounted in the organ bath, then the developed tension was recorded. Histologically, the aged bladder did not show pathologic changes such as inflammation and hypertrophy. Carbachol-induced contraction in aged rat bladder was identical to that obtained in young rat. In the receptor binding assay, [3H]QNB maximal binding capacity and Kd value were not significantly changed in aged bladder. In contrast, a selective α-adrenergic agonist phenylephrine, elicited greater contractions both in the aged body and trigone than those in young rats. The augmentation of α-adrenoceptor-mediated contractions in aged bladder may induce urinary dysfunction such as voiding difficulty.

Alpha1B adrenoceptor expression is a marker of reduced survival and increased tumor recurrence in patients with endometrioid ovarian cancer

AIM: To investigate the expression patterns of different adrenoceptor isoforms in ovarian cancer and their association with survival and tumor recurrence. METHODS: The protein expression levels of a1 B, a2 C and b2 adrenoceptor were assessed in unselected ovarian cancer using immunohistochemistry on microarrayed archival tissue samples. A database containing clinical and pathology parameters and follow-up was usedto investigate the association between adrenoceptor isoform expression with ovarian specific survival and tumor recurrence, using univariate and multivariate statistical analysis. RESULTS: Expression of a1 B showed an association with reduced ovarian specific survival(P = 0.05; CI: 1.00-1.49) and increased tumor recurrence(P = 0.021, CI: 1.04-1.69) in the whole patient group. On subanalysis the expression of a1 B in endometrioid cancers(χ2 = 5.867, P = 0.015) was found to predict reduced ovarian specific survival and increased tumor recurrence independently of tumor grade, clinical stage and chemotherapy. An association with clinical outcome was not seen for a2 C or b2 AR.CONCLUSION: Alpha1 B adrenoceptor protein was found to predict increased risk of tumor recurrence and reduced mortality in patients with endometrioid type ovarian cancer and should be investigated as a biomarker for identifying patients at increased risk of disease progression. Furthermore, a adrenergic receptor antagonists with a1 B selectivity should be investigated as a possible adjuvant therapy for treating patients with endometrioid cancer. Proof of principle could be tested in a retrospective population study.

Evidence for a Non-<i>β</i>₂-Adrenoceptor Binding Site in Human Lung Tissue for a Subset of <i>β</i>₂-Adrenoceptor Agonists

The aim of this study was to compare the binding profile of a range of β2-adrenoceptor (β2-AR) agonists and antagonists in human lung tissue. Radioligand saturation and competition binding experiments were performed by filtration with a β2-AR antagonist ([3H]propranolol) or agonist ([3H]vilanterol) radioligand and membrane fragments generated from lung parenchyma in the presence of 100 μM guanosine 5’-[β,γ-imido]triphosphate (Gpp(NH)p). In membranes prepared from human lung parenchyma, carmoterol, formoterol, ICI118551, propranolol and salbutamol resulted in inhibition of [3H]vilanterol binding to levels that were significantly different from indacaterol, salmeterol and vilanterol (ANOVA, Bonferroni post-test, P < 0.001 except formoterol vs indacaterol where P < 0.01). Indacaterol and salmeterol resulted in inhibition of [3H]vilanterol binding to levels that were not significantly different from vilanterol (ANOVA, Bonferroni post-test, P > 0.05). Indacaterol, salmeterol and vilanterol resulted in full inhibition of [3H]propranolol binding to levels not significantly different from ICI118551 (ANOVA, Bonferroni post-test, P > 0.05). Indacaterol, salmeterol and vilanterol bind to an additional site in human lung parenchyma membranes that is distinct from the β2-AR.

The Expression of β3-adrenoceptor of Left Ventricle and the Effect on Heart Function by Stimulating β3-AR in Rats With Experimental Heart Failure

Objectives To observe the expression of β3-adrenoceptor （β3-AR） of left ventricle and the effect on heart function by stimulating β3-AR in rats with experimental heart failure. Methods Rats were randomly divided into heart failure group and control group. Heart failure models were built up by ligating coronary artery in rats. The expression of β3-AR mRNA were detected with RT-PCR; The change of heart function were observed after administration of BRL37344 （β3-AR agonist） by measuring left ventricular end-systolic pressure （LVESP）, left ventricular end-diastolic pressure （LVEDP）, the maximum pressure ascending rate of left ventricle （＋dp/ dtmax） and the maximum pressure descending rate of left ventricle（-dp/dtmax）. Results The expression of β3-AR mRNA （β3/β-actin） was 0.028±0.005 and the proportion of β3-AR （β3/β1＋β2＋β3） was 5.4%±0.06% in failure rats while the expression of β3-AR mRNA was 0.011 ±0.004 and the proportion was 1.2%±0.04% in control rats; The descending percentage of LVESP, ＋ dp/dtmax and -dp/dtmax were 16.1%, 21.7% and 13.2% respectively with administration of BRL37344 in failure rats, while 12.2%, 15.8% and 11.5% in control rats. Conclusions Compared with control group the expression of β3-AR mRNA of left ventricle was obviously increased and the negative inotropic function with exciting β3-AR was obviously enhanced in failure groups.

Onset Time Profiles for Syncope Associated with <i>α</i>₁-Adrenoceptor Blockers in Males: Analysis of a Spontaneous Adverse Drug Event Database

Background: α1-Adrenoceptor blockers (α1Bs) are used for the treatment of benign prostatic hyperplasia and hypertension, but they are known to cause hypotension-related adverse events. The objective of the present study was to evaluate the onset time profiles for syncope associated with the use of α1Bs. Methods: We analyzed the data obtained from?the Japanese Adverse Drug Event Report (JADER) database for a period from April 2004 until November 2016 and calculated reporting odds ratios (RORs) for eight α1Bs available on the Japanese market, using disproportionality analysis. Moreover, time information recorded in the JADER database was analyzed to evaluate the onset times of adverse events. Results: In total, 186,724 reports for males older than 20 years were analyzed. Significant RORs for syncope, with 95% confidence intervals, were obtained for naftopidil (2.53, 1.81 - 3.53), silodosin (4.24, 2.37 - 5.20), and tamsulosin (2.22, 1.75 - 2.81). The median onset times of syncope for naftopidil, silodosin, and tamsulosin were 37, 26, and 108 days, respectively. The shape parameters obtained by fitting the data for the three α1Bs to the Weibull distribution were all less than 1.0, indicating that all these drugs could be classified as the early failure type. The cumulative incidence rates showed that the onset times of syncope tended to be similar among the three α1Bs. Conclusions: Patients treated with selective α1Bs should be closely monitored for 100 days, especially in the first 20 to 40 days after initiation of silodosin or naftopidil. This information may be useful for patients and healthcare professionals in preventing syncope due to the use of selective α1Bs.

Clonidine Inhibits Phenylephrine-Induced Contraction of Rat Thoracic Aortae by Competitive Antagonism of α₁-Adrenoceptors Independent of α₂-Adrenoceptor Stimulation

Clonidine is a classically categorized α2-adrenoceptor (α2-AR) agonist that produces vascular contractions by stimulating arterial smooth muscle α2-ARs. However, clonidine inhibits α1-AR-mediated arterial contractions. Recently, it was suggested that repeated stimulation with clonidine induces desensitization of α2-ARs, thus inhibiting noradrenaline-induced smooth muscle contractions. In the present study, we examined whether clonidine-mediated inhibition of α1-AR contractions involves interactions with α2-ARs in rat thoracic aortae. 1) Clonidine and guanfacine inhibited electrical field stimulation-induced contractions in a concentration-dependent, yohimbine-sensitive manner in isolated rat vas deferens preparations. 2) Clonidine almost completely suppressed phenylephrine-induced sustained contractions of rat thoracic aortae. 3) Clonidine competitively inhibited phenylephrine-induced contractions with a pA2 value of 6.77 at concentrations between 10-7 and 10-6 M. At 10-5 M, clonidine inhibited phenylephrine-induced contractions and dramatically reduced maximum contractions. 4) In contrast, clonidine did not inhibit contractions produced by high KCl or prostaglandin F2α. 5) Inhibition of phenylephrine-induced sustained contractions by clonidine was also produced in the presence of yohimbine. However, guanfacine did not inhibit phenylephrine-induced sustained contractions. These findings suggest that clonidine inhibits phenylephrine-induced contraction of rat thoracic aortae by competitive antagonism of α1-ARs, which is mediated through a mechanism independent of α2-AR stimulation.

Effect of β_3-adrenoceptors on Ventricle Fibrillation Threshold and Effective Refractory Period in Rats With Heart Failure

Objectives To observe the effect of β3-Adrenoceptor （AR） on ventricle fibrillation threshold （VFT） and effective refractory period （ERP） in rats with heart failure. Methods Rats were randomized into control group and heart failure group. The expression of β3-ARmRNA was detected with RTPCR; The VFT, ERP, LVESP,LVEDP, ＋dp/dtmax and -dp/dtmax was measured at the same time with administration of BRL37344 （ 2 nmol / kg, β3- AR agonist）. Results ①Both the expression of β3-AR mRNA and the proportion increased in rats with heart failure in comparison with control rats （0.028 vs. 0.011 and 5.4% vs 1.2%, P 〈 0.05）;② ERP was longer in rats with heart failure than control group （70.5±5.5 ms vs 59.5±6.4ms, P 〈 0.05） and there was no difference of ERP in rats with heart failure with administration of BRL37344 （73.0±4.8 ms vs 70.5± 5.5 ms, P 〉0.05）; ③VFT was lower in rats with heart failure than control group（10.9±0.8 mv vs 30.5± 1.3 mv, P〈 0.05） and decreased obviously in rats with heart failure with administration of BRL37344 （7.1±0.6 mv vs 10.9±0.8 mv, P 〈 0.05） ; The decrease of VFT correlated with the effect on LVESP, ＋dp/ dtmax,-dp/dtmax of BRL37344 and the expression of β3-AR mRNA （correlation coefficient： 0.788, 0.708, 0.759, 0.787; P 〈 0.05）. Conclusions The expression of β3-AR mRNA of left ventricle was obviously increased in rats with heart failure, and activation of β3-AR had no effect on ERP but could decreased VFT which correlated with the effect of β3-AR on LVESP, ＋dp/dtmax, -dp/dtmax and the expression of β3-AR mRNA.