AduoLa Fuzhenglin Down-regulates Microwave-induced Expression of β_1-adrenergic Receptor and Muscarinic Type 2 Acetylcholine Receptor in Myocardial Cells of Rats

This paper is aimed to study the effect of ADL on expression of ~z-AR and Mz-AchR in myocardial cells of rats exposed to microwave radiation. Immunohistochemistry, Western blot and image analysis were used to detect the expression of ~I-AR and Mz-AchR in myocardial cells at 7 and 14 d after microwave exposure. The results show that the expression level was higher in microwave exposure group and 0.75 g/（kg.d） ADL group than in sham operation group and significantly lower in 1.5 and 3.0 g/（kg.d） ADL groups than in microwave group. So we have a conclusion that the expression of I^z-AR and Mz-AchR is down-regulated in myocardial cells of rats exposed to microwave radiation. ADL can protect rats against microwave-induced heart tissue injury.

Blocking beta 2-adrenergic receptor inhibits dendrite ramification in a mouse model of Alzheimer's disease

Dendrite ramification affects synaptic strength and plays a crucial role in memory. Previous studies revealed a correlation between beta 2-adrenergic receptor dysfunction and Alzheimer＇s disease （AD）, although the mechanism involved is still poorly understood. The current study investigated the potential effect of the selective β2-adrenergic receptor antagonist, ICI 118551 （ICI）, on Aβ deposits and AD-related cognitive impairment. Morris water maze test results demonstrated that the performance of AD-transgenic （TG） mice treated with ICI （AD-TG/ICI） was significantly poorer compared with NaCl-treated AD-TG mice （AD-TG/NaCl）, suggesting that β2-adrenergic receptor blockage by ICI might reduce the learning and memory abilities of mice. Golgi staining and immunohistochemical staining revealed that blockage of the β2-adrenergic receptor by ICI treatment decreased the number of dendritic branches, and ICI treatment in AD-TG mice decreased the expression of hippocampal synaptophysin and synapsin 1. Western blot assay results showed that the blockage of β2-adrener- gic receptor increased amyloid-β accumulation by downregulating hippocampal a-secretase activity and increasing the phosphorylation of amyloid precursor protein. These findings suggest that blocking the β2-adrenergic receptor inhibits dendrite ramification of hippocampal neurons in a mouse model of AD.

Association of β3 Adrenergic Receptor and Peroxisome Proliferator-activated Receptor Gamma 2 Polymorphisms With Insulin Sensitivity:A Twin Study

Objective To study the effect of β3 adrenergic receptor （β3AR） Trp64Arg and peroxisome proliferator activated receptor gamma 2 （PPAR72） Prol2Ala polymorphisms on insulin resistance. Methods One hundred and eight dizygotic twin pairs were enrolled in this study. Microsatellite polymorphism was used to diagnose zygosity of twins. Insulin sensitivity was estimated with logarithm transformed homeostasis model assessment （HOMA）. PCR-RFLP analysis was performed to detect the variants. As a supplement to the sib-pair method, identity by state （IBS） was used to analyze the association of polymorphisms with insulin sensitivity. Results The genotype frequencies of Trp64Trg, Trp64Arg, and Arg64Arg were 72.3%, 23.8%, and 3.9%, respectively, while the genotype frequencies of Pro12Pro, Pro12Ala, and Ala12Ala were 89.9%, 9.6%, and 0.5%, respectively. For β3AR Trp64Arg the interclass co-twin correlations of Waist-to-hip ratio （WHR）, blood glucose （GLU）, and insulin （INS）, homeostasis model assessment insulin resistance index （HOMA-IR） of the twin pairs sharing 2 alleles of IBS were greater than those sharing 0-1 allele of IBS, and HOMA4R had statistic significance. For PPAR3t2 Prol2Ala most traits of twin pairs sharing 2 alleles of IBS had greater correlations and statistic significance in body mass index （BMI）, WHR, percent of body fat （PBF） and GLU, but there were low correlations of either insulin or HOMA-IR of twin pairs sharing 1 or 2 alleles of IBS. The combined effects of the two variations showed less squared significant twin-pair differences of INS and HOMA-IR among twins sharing 4 alleles of IBS. Condusions β3AR Trp64Arg and PPAR）,2 Pro 12Ala polymorphisms might be associated with insulin resistance and obesity, and there might be slight synergistic effects between this two gene loci, and further studies are necessary to confirm this finding.

Clinical value of detecting autoantibodies against β1-, β2-, and α1-adrenergic receptors in carvedilol treatment of patients with heart failure

Objective To determine the possible association of anti-β1-adrenergic receptors(anti-β1-AR), anti-β2-AR and anti-α1-AR with carvedilol treatment in patients with heart failure(HF). Methods A total of 267 HF patients were prospectively enrolled. Blood samples were measured by an enzyme-linked immunosorbent assay. All of the patients received carvedilol for their HF. Each patient was followed up for six months and their cardiac function was measured. Results The final analysis encompassed 137 patients comprising 65 patients with three autoantibodies(positive group) and 72 patients without all three autoantibodies but with one or two autoantibodies(negative group). The frequency and geometric mean titer of anti-β1-AR, anti-β2-AR, and anti-α1-AR were significantly lower in the group without all three autoantibodies after six months of carvedilol treatment(all P < 0.01;from 100% to 57%, 50%, and 49%, respectively;and from 1: 118, 1: 138, and 1: 130 to 1: 72, 1: 61, and 1: 67, respectively). Furthermore, 28 patients in the positive group demonstrated complete ablation of autoantibodies. In addition, left ventricular remodelling and function was significantly improved by the use of carvedilol combined with the standard treatment regime for six months in the positive group(P < 0.01) when compared to the negative group(P < 0.05). Conclusions Carvedilol treatment significantly decreases frequency and geometric mean titer in patients with all three autoantibodies, even up to complete ablation, and significantly improved cardiac function and remodelling. The effect of carvedilol is probably correlated to the presence of all three autoantibodies.

Relationship between catecholamine level and gene polymorphism of β1 adrenergic receptor G1165C in children with EV71 infection in hand foot and mouth disease

Objective:To investigate the relationship between the levels of plasma adrenaline and norepinephrine and gene polymorphism of β1 adrenergic receptor G1165 C in children with enterovirus 71(EV71) infection in hand foot and mouth disease(HFMD). Methods:The polymerase chain reaction(PCR) was used to detect the expression of gene polymorphism of β1 adrenergic receptor G1165 C in vitro. The levels of plasma adrenaline and norepinephrine were measured by enzyme-linked immunosorbent assay(ELISA). Results:The plasma norepinephrine level of severe group was significantly higher than the mild group in children with EV71 infection in HFMD(P<0.05); however,the levels of plasma adrenalinein in two groups had no statistical differences(P>0.05); There was no significant difference in the distribution of β1 adrenergic receptor G1165 C genotype and allele between EV71 infection group and healthy control group(P> 0.05). Further analysis of EV71 infection group by dividing it into mild and severe groups showed that there was no significant difference in the distribution of genotype and allele between these two groups as well(P> 0.05). There was no significant difference in the levels of epinephrine and norepinephrine in different genotypes of EV71 infection group(P> 0.05),and in the levels of plasma epinephrine and norepinephrine in the mild and severe groups(P> 0.05). Conclusions:As the disease gets worse,the plasma norepinephrine level has a rising trend in children with EV71 infection in HFMD,which is an important indicator to evaluate the progress of the disease. However,the gene polymorphism of eptor G1165 C have no significant correlation,not only with the susceptibility and severit β1 adrenergic recy of EV71 infection in hand,foot and mouth disease,but also with the levels of catecholamine.

Association between essential hypertension and polymorphisms of beta 1 adrenergic receptor gene G1165C (Gly389Arg) in Chinese Mongolian population

BACKGROUND： The prevalences of hypertension, cerebrovascular diseases, etc. are higher in Mongolian population because of the influence of various factors including genetics, geography, diet, etc. Therefore, it is helpful to develop researches on the genetics of various diseases including hypertension in Mongolian population. OBJECTIVE： To analyze the association between the polymorphism of beta1 adrenergic receptor （β1-AR） gene G1165C （Arg389Gly）, an important candidate gene for various diseases of cardiovascular system, and essential hypertension in Mongolian population. DESIGN ： A cross-sectional study SETTINGS： Department of Neurology, the First Affiliated Hospital of Inner Mongolia Medical College; Wulate Houqi Red Cross Society. PARTICIPANTS： The survey was carried out from February 2003 to March 2005. Totally 239 Mongolian residents, whose blood relations of 3 generations were all Mongolians, were selected from Wulate Houqi, Inner Mongolia, and they were all informed with the survey and detected items. Based on the diagnostic standard of hypertension set by WHO in 1999, the subjects were divided into two groups according to the level blood pressure： ① Normal blood pressure group （n=117）： systolic blood pressure （SBP） 〈 140 mm Hg （1 mm Hg =0.133 kPa）, diastolic blood pressure （DBP） 〈 90 mm Hg, and those having histories of cerebrovascular disease, heart disease, diseases of liver, kidney and tiroides, and diabetes mellitus were excluded. ② Essential hypertension group （n=122）： including 51 patients with simple high SBP. All the enrolled subjects had no blood relationship with each other, and had no history of miscegenation. METHODS ： The body height, body mass, waist circumference and blood lipids were measured routinely, and their habits of smoking and drinking were also investigated. Penpheral venous blood （5 mL） was drawn, the genome DNA was extracted, and the polymorphisms of the β1-AR Gl165C （Gly389Arg） genotype were detected with the Sequenom system. Polymerase chain reaction （PCR） experiment and SNP detection were performed in Huada Gene Laboratory of Bejing, then the univariate analysis of variance was applied in the sample comparison among groups, and the chi-square test was used to compare the genotypes and allele frequencies. The odd ratio （OR） and 95% confidence interval （CO were calculated. MAIN OUTCOME MEASURES： The distributions of β1-AR Gl165C （Gly389Arg） genotypes and alleles were observed. RESULTS： A11 the 239 subjects were involved in the analysis of results, and no one missed, ①Comparison of β1-AR G1165C （Gly389Arg） genotypes and allele distnbutions： In Mongolian population, the frequencies of CC and GG＋GC genotypes at β1-AR G1165C （Gly389Arg） site in the essential hypertension group （72%, 28%） were not significantly different from those in the normal blood pressure group （67%, 33%） （xz=0.841, P=-0.359; OR 0.773, 95%Cl： 0.445-1.342）; The frequencies of C and G alleles also had no significant differences between the essential hypertension group （85%, 15%） and the normal blood pressure group （82%, 18%） （x^2=1.136, P=-0.287; OR： 0.769, 95%Cl： 0.747-1.248）. ②The frequencies of CC and GG＋GC genotypes at β1-AR G1165C （Gly389Arg） site had no significant differences between the patients with simple high SBP （71%, 29%） and the normal blood pressure group （x^2=0.250, P=-0.617; OR： 0.833, 95%C/： 0.408-1.703）; The frequencies of C and G alleles were not significantly different between the patients with simple high SBP （86%, 14%） and the normal blood pressure group （x^2=0.670, P=-0.413; OR 0.766, 95%Cl： 0.404-1.453）. CONCLUSION： In Mongolian population, the distributions of the genotypes and alleles of β1-AR Gl165C （Gly389Arg） have no obvious differences between the subjects with normal blood pressure and the patients with essential hypertension （including simple SBP increase）, which suggests that G1165C （Glu389Asp） site of β1-AR gene may be not a genetic mark of essential hypertension and simple high SBP in Mongolian population.

β_(2) and α_(2) adrenergic receptors mediate the proneurogenic in vitro effects of norquetiapine

Positive modulation of adult hippocampal neurogenesis may contribute to the therapeutic effects of clinically relevant antidepressant drugs,including atypical antipsychotics.Quetiapine,an antipsychotic which represents a therapeutic option in patients who are resistant to classical antidepressants,promotes adult hippocampal neurogenesis in preclinical studies.Norquetiapine,the key active metabolite of quetiapine in humans,has a distinctive receptor profile than the parent compound.The drug is indeed a high affinity norepinephrine transporter inhibitor and such activity has been proposed to contribute to its antidepressant effect.At present,no information is available on the effects of norquetiapine on adult neurogenesis.We extensively investigated the activity of quetiapine and norquetiapine on adult murine neural stem/progenitor cells and their progeny.Additionally,selective antagonists for β_(2)/α_(2) adrenergic receptors allowed us to evaluate if these receptors could mediate quetiapine and norquetiapine effects.We demonstrated that both drugs elicit in vitro proneurogenic effects but also that norquetiapine had distinctive properties which may depend on its ability to inhibit norepinephrine transporter and involve β_(2)/α_(2) adrenergic receptors.Animal care and experimental procedures were approved by the Institutional Animal Care and Use Committees(IACUC)at University of Piemonte Orientale,Italy(approval No.1033/2015PR)on September 29,2015.

Expression of hippocampal adrenergic receptor mRNA in a rat model of depression

Adrenergic receptor dysfunction is suggested as a potential cause of hippocampal vulnerability to stress-related pathology. We examined mRNA expression of adrenergic receptor （AR） subtypes α1-AR, α1-AR, and β1-AR in hippocampal subregions （CA1, CA3, dentate gyrus） using in situ hybridization in a depression model induced by chronic unpredictable mild stress and social isolation, α1-AR mRNA expression was significantly increased in the CA3 and dentate gyrus, β1-AR mRNA was significantly increased in the CA1, and α1-AR mRNA remained unchanged in all regions of depression rats compared with controls. Thus, different AR subtypes exhibit a differing pattern of mRNA expression in various hippocampal subregions following depression.

Age-associated alternations in cardiac β-adrenergic receptor signaling

During aging, cardiac contractile response to β-AR stimulation is decreased in humans and animal models. Recent studies demonstrate that the positive inotropic effects of both β1-AR and β2-AR stimulation are significantly decreased with aging.This is accompanied by decreases in both β-AR subtype densities and a reduction in membrane adenylyl cyclase activity. However,neither G protein-coupled receptor kinases (GRKs) nor inhibitory G proteins (Gi) appears to contribute to the age-associated reduction in the β-AR modulation of contraction. Thus, while both aging and chronic heart failure exhibit a diminution in cardiac β-AR responsiveness, only heart failure exhibits increased GRK-mediated desensitization ofβ-Ars and an upregulation of Gi proteins.

Association of Polymorphisms of β_3-Adrenergic Receptor,Angiotensinogen and Angiotensin- Converting Enzyme Gene with Hypertension in type 2 DM

ObjectiveTo explore the relationship between the mutant genes of ACE,ATN,β 3 AR and hypertension in patients with type 2 DM. Methods281 recruited Chinese subjects were divided into two groups according to the oral glucose tolerance test (OGTT): ① non diabetes group including normal and impaired glucose tolerance (NGT,IGT): 169 cases;② Type 2 diabetes mellitus (DM): 112 cases. The subjects were genotyped for the ACE gene,the ATN gene and the codon 64 of β 3 AR gene polymorphisms by applying polymerase chain reaction (PCR),PCR restriction fragment length polymorphisms screening with the use of endonuclease. ResultsOur study found that the frequency of D/D genotype and D allele of ACE gene,a/a genotype and an allele of ATN gene in HT patients without DM were increased (P all <0.05);that the frequency of codon 64 mutation of β 3 AR gene also increased in HT patients with NGT (P < 0.05 ). In the model of multiple factors non condition al Logistic regression analyses,HT had relationship with history of hypertension,age and glucose tolerance (OR=10.745 7,1.780 4, 2.034 6;P=0.000 4, 0.000 0 ,0.024 6;respectively),with polymorphism of ATN gene,β 3AR gene,ACE gene (OR= 2.273 6 ,1.935 3,1.830 9;P=0.054 3,0.028 7,0.043 2;resceptively). ConclusionThese results suggest that variants of ACE gene,β 3AR gene,ATN gene were associated with HT in type 2 DM.

Effects of Shexiangbaoxin pills on the expression of cardiac α1- and β-adrenergic receptor subtypes in rat hearts with heart failure induced by myocardial infarction

Background Chronic heart failure （CHF） had been characterized as an activated sympathetic system leading to the alteration of adrenergic receptor （AR） levels in the heart. Thus far, not much research has been done with regard to traditional Chinese medical treatment for CHF. We investigated the effect of Shexiangbaoxin pills （SXBXP） on the function of the heart and the expression of a1-AR and b-AR subtypes in the messenger RNA （mRNA） levels and protein levels of non-infarction left ventricular tissue from rats with CHF induced by myocardial infarction.Methods Models of CHF were established by left anterior descending coronary artery ligature. Fifty-four Wistar rats were randomly divided into five groups： normal control group （group A）, sham operation group （group B）, CHF model group （group C）, positive medicine control group （group D）, and small-dose SXBXP group （group E） and large-dose SXBXP group （group F）, deployed intragastrically. Cardiac function was examined by echocardiography before and after therapy; mRNA expressed levels were measured by semiquantitative reverse transcription polymerase chain reaction （RT-PCR） for b1-AR, b2-AR, b3-AR, a1A-AR, a1B-AR, and a1D-AR; protein levels were measured by Western blotting analysis for b1-AR, b2-AR, a1A-AR, a1B-AR, and a1D-AR in non-infarction left ventricular tissue.Results There was no significant difference in the left ventricular ejection fraction （LVEF） between groups A and B. Compared to group B, LVEF of groups C, D, E, and F were significantly decreased （P 〈0.01） before therapy. After therapy, compared to group C, LVEF of group F was significantly improved （P 〈0.05）. Compared to group B, b1-AR and a1B-AR expressed levels were markedly decreased （P 〈0.05）, a1A-AR and b3-AR were significantly increased （P 〈0.01） in group C, and in both mRNA and protein expressed levels b2-AR had no significant difference between groups B and C （P 〉0.05）. a1D-AR mRNA levels were unchanged in each group （P 〉0.05）, but a1D-AR protein level was significantly decreased in group C （P 〈0.05）. After treatment, compared to group C, mRNA levels of b1-AR and a1B-AR were significantly increased （P 〈0.05 and P 〈0.01）, and a1A-AR was markedly decreased in groups D, E, and F （P 〈0.05）. b3-AR level significantly declined in both groups D and F （P 〈0.01）, but b2-AR and a1D-AR expressed levels remained unchanged in each group （P 〉0.05）. Protein levels, compared to group C, b1-AR was significantly increased （P 〈0.01, P 〈0.05, and P 〈0.01） and a1A-AR was markedly decreased in groups D, E, and F （P 〈0.05, P 〈0.01, and P 〈0.01）. b2-AR expressed level was significantly increased in group F （P 〈0.05）. a1B-AR expressed level was significantly increased in both groups E and F （P 〈0.05）, and a1D-AR was remarkably increased in both groups D and F （P 〈0.05）.Conclusions After SXBXP treatment, LVEF was increased and cardiac function was significantly ameliorated in rats with CHF. The therapeutic effect of SXBXP may be related to better blood supply for myocardium and up-regulation of b1-AR and a1B-AR, and down-regulation of a1A-AR and b3-AR. The results show that SXBXP can be used in treatment of CHF and the therapeutic effect of large-dose SXBXP is superior to small-dose SXBXP.

Effects of metoprolol on β1 adrenergic receptor polymorphism and receptor density in urban Chinese patients with heart failure

β-blockers have been recommended as a standard treatment for patients with mild to moderate systolic chronic heart failure （CHF） because they not only relieve patients＇ symptoms but also decrease mortality. However, β-blockers have a variety of effects on different CHF patients. Among them, β1-adrenergic receptor （AR） gene polymorphism is probably a significant one. The purpose of this study was to investigate the effects of metoprolol on cardiac function, cardiac geometrical size and density of β1-AR of CHF patients as well as the association between two common single nucleotide polymorphisms （SNPs） of β1-AR（Gly389Arg and Ser49Gly） and the effects of metoprolol.

Jueming Prescription(决明方) Reduces Body Weight by Increasing the mRNA Expressions of Beta3-Adrenergic Receptor and Uncoupling Protein-2 in Adipose Tissue of Diet-Induced Obese Rats

Objective： To investigate the antiobesity effect of Jueming Prescription （决明方, JMP）, a Chinese herbal medicine formula, and its influence on mRNA expressions of beta3 adrenergic receptor （beta3-AR） and uncoupling protein-2 （UCP-2） in adipose tissue of diet-induced obese rats. Methods： Fifty male Sprague-Dawley rats were randomly divided into the normal control group （n=8） that was on a standard chow diet, and the obese model group （n=42） that was on a diet of high fat chow. Two weeks after the high fat diet, 29 obese rats in the obese model group were further randomly divided into 3 groups： the untreated obese model group （n=9）, the met＇formin group （n=10, mefformin 300 mg-kg-1.day-1）, and the JMP group （n=10, JMP 4 g.kg-1.dayl）. After 8-week treatment, body weight, wet weight of visceral fat, and percentage of body fat （PBF） were measured. The levels of fasting blood glucose, serum lipids, and insulin were assessed, and insulin sensitivity index （ISI） was calculated. The adipose tissue section was stained with hematoxylin-Eosin, and the cellular diameter and quantity of adipocytes were evaluated by light microscopy. The mRNA expressions of beta3-AR and UCP-2 from the pet-renal fat tissue were determined by real-time reverse transcription polymerase chain reaction （RT-PCR）. Results： Compared with the obese model group, treatment with JMP resulted in significantly lower body weight, wet weight of visceral fat, PBF, and diameter of adipocytes, and significantly higher level of high-density lipoprotein cholesterol, ISI （all P〈0.01）, JMP increased the mRNA expressions of beta3-AR and UCP-2 from pedrenal fat tissue （P〈0.05, P〈0.01）. Conclusions： JMP could reduce body weight and adipocyte size; and the effect was associated with the up-regulation of beta3-AR and UCP-2 expressions in the adipose tissue and improvement of insulin sensitivity.

Yohimbine protects against endotoxin-induced acute lung injury by blockade of alpha 2A adrenergic receptor in rats

Background Alpha 2A adrenergic receptor （AR） is a subtype of （]2 AR belonging to G protein-coupled receptors, and exerts a variety of biological effects. Recent studies have demonstrated that the a2A AR activation was closely related with inflammatory reaction. The present study aimed to investigate the influence of a2A AR antagonist, yohimbine, on the severity of endotoxin-induced acute lung injury in rats.

Correlation Analysis between Visceral Manifestation Theories on Xuanfa and Effect of Adrenergic Receptors

Chinese visceral manifestation theory states that lung dominates qi,regulates breathing,and governs Xuanfa（dispersing）and Sujiang（descending）.Clarifying this theory with modern physiological and pathological knowledge has been considered as an important part of complementary and alternative medicine therapy.Previous studies found that most Xuanfa drugs contained pharmacodynamic ingredients related to adrenergic receptors（ARs）signal transduction.The association of Xuanfa,with the control of breath movement,nutrient transfer,spreading heat to regulate temperature,and helping the heart control blood circulation,coincides with the physiological function of organs dominated by ARs-regulated sympathetic postganglionic fibers.Therefore,we hypothesize that Xuanfa is closely related to ARs-regulated signal transduction.By modern biological knowledge,we tried to evaluate and expound the correlation between the molecular mechanisms of modern physiology or pathology and Xuanfa or Sujiang theory.Ultimately,the research and development of modern drugs should fully expect the guidance from Chinese visceral manifestation theory,and the application of this principle will guide the prevention and clinical treatment of a variety of refractory diseases caused by a change in environment,climate,or lifestyle.

Nitric Oxide Formation Contributes toβ-adrenergic Dilation of Epicardial Coronary Arteries in Response to Intravenous Administration of Dobutamine in Dogs

To examine the role of nitric oxide in the β-adrenergic vasodilation of epicardial coronary arteries in dogs, 12 dogs were instrumented for measurement of left anterior descending coronary artery diameter by transthoracic echocardiography before and after dobutamine (5 μg/kg/min IV) with and without intracoronary infusion of N G-monomethyl-L-arginine (L-NMMA) (1 mg/kg). In all 12 dogs, the diameter of left anterior descending coronary artery increased significantly from 2.35±0.25 mm to 2.59±0.24 mm (P<0.001) after dobutamine administration. In 6 of the 12 dogs, the percent change in left anterior descending coronary artery diameter induced by dobutamine decreased significantly from 12.5%±8.6% to -1.5%±5.4% (P<0.05) after the administration of intracoronary L-NMMA (1 mg/kg for 5 min) to block nitric oxide synthesis from L-arginine. The study demonstrated that nitric oxide formation contributes to the β-adrenergic dilatory response of epicardial coronary arteries to dobutamine in dogs.

Role of β-Adrenergic Signal Transduction Pathway on Myocardial Ischemic Preconditioning of Rats

To study the changes in every part of the β-adrenergic signal transduction pathway and their effects on ischemic preconditioning of rat myocardium in vivo. SD rats were divided into three groups： IP group, I/R group and CON group. The IP group was further divided into PC1-, 2-, 3-, and PC1＋, 2＋, 3＋ groups according to preconditioning procedure. The rats received surgical procedure and underwent left coronary artery occlusion and reperfusion. We analyzed the infarct size by TTC staining, measured serum myocardial enzymes, studied the β-AR Bmax and Kd by radioligand binding assay of receptors, checked the activity of AC and PKA by the method of biochemistry and examined the content of cAMP by radioimmunoassay. The infarct area was much smaller in the IP group than in the I/R group （P〈0. 001）, while the enzymes were significantly higher in I/R （P〈0. 001）. The Bmax of β-AR in IP was much higher than that in I/R （P〈0. 001）, but no difference in Kd could be seen between IP and I/R groups. In IP, the activity of AC and PKA and the content of cAMP were higher than those in I/R （P〈0.05, 0. 002 and 0. 001, respectively）. In the procedure of preconditioning, the content of cAMP and the activity of PKA showed the characteristic of cyclic fluctuation. Ischemic preconditioning can protect the heart from necrosis and reduce endo-enzyme leakage. The system of β-adrenergic signal transduction pathway probably takes part in the protection effect of the IP, which might be elicited by the PKA .

肾上腺素、去甲肾上腺素刺激培养的大鼠心肌细胞凋亡

目的 :观察肾上腺素 ( AD)或去甲肾上腺素 ( NA)刺激体外培养的大鼠心肌细胞凋亡 ,探讨其作用机制。方法 :大鼠心肌细胞分别暴露于 10 - 7mol/L 的 NA,10 - 7m ol/L 的 AD,NA+酚妥拉明 ( 10 - 7m ol/L) ,NA+艾司洛尔 ( 10 - 7mol/L) ,AD+酚妥拉明 ( 10 - 7m ol/L)或 AD+艾司洛尔 ( 10 - 7mol/L) 2 4 h。流式细胞仪检测凋亡水平。结果 :NA使凋亡细胞百分率由 ( 4 .2± 1.6) %增加到 ( 10 .0± 5 .0 ) % ( P<0 .0 1;n=8) ,此作用可被艾司洛尔完全抑制 ,而不受酚妥拉明影响。AD与 NA的作用相仿 ,使凋亡细胞百分率增加到 ( 12 .8± 7.9) % ,且 AD诱导的凋亡同样被艾司洛尔完全抑制但不受酚妥拉明的影响。结论 :AD和 NA可能通过激活 β肾上腺素能通路 。

Effect of tamsulosin on ejaculatory function in BPH/LUTS

This study was undertaken to determine the impact on ejaculatory function of tamsulosin （0.2 mg） given once daily （OD） for 12 weeks and to identify risk factors for ejaculatory dysfunction in patients undergoing this treatment. Males with an International Prostatic Symptom Score （IPSS） ≥ 8 were enrolled in this study. All participants completed questionnaires, including the IPSS and the Male Sexual Health Questionnaire （MSHQ）, and serum prostate-specific antigen, transrectal ultrasound and uroflowmetry with post-void residual were measured. After initiating 0.2 mg OD tamsulosin, patients were re-evaluated on the fourth and twelfth weeks of medication. The chi-squared test, the independent t-test and one-way ANOVA were used to compare means. Binary logistic regression analysis was used to calculate the odds ratio for all risk factors. A total of 177 men constituted the study cohort. No significant difference was observed between baseline and follow-up for the erectile function, ejaculatory function, satisfaction, sexual activity and desire domains （EFD, EjFD, SDA and ADD） or for erectile or ejaculatory bother mean scores. After 12 weeks, the overall incidence of ejaculatory dysfunction （EjD） was 13.4%. Incidences of the seven different types of EjD （decreased frequency, delay, dryness, decreased strength/force, decreased volume, decreased pleasure and pain at ejaculation） were 2.4%, 3.1%, 3.9%, 3.9%, 6.3%, 7.1% and 3.1%, respectively. Baseline EjFD scores were higher for I PSS responders than for non-responders （26.09 vs. 24.06, P=0.03）. An EjFD score reduction was more frequent in IPSS responders. The incidence of EjD was small, but not negligible and was more frequent in patients with less lower urinary tract symptoms, a smaller prostate, higher baseline MSHQ totals and higher EjFD scores.

Cardiac autonomic nerve distribution and arrhythmia

OBJECTIVE： To analyze the distribution characteristics of cardiac autonomic nerves and to explore the correlation between cardiac autonomic nerve distribution and arrhythmia. DATA RETRIEVAL： A computer-based retrieval was performed for papers examining the distribution of cardiac autonomic nerves, using “heart, autonomic nerve, sympathetic nerve, vagus nerve, nerve distribution, rhythm and atrial fibrillation” as the key words. SELECTION CRITERIA： A total of 165 studies examining the distribution of cardiac autonomic nerve were screened, and 46 of them were eventually included. MAIN OUTCOME MEASURES： The distribution and characteristics of cardiac autonomic nerves were observed, and immunohistochemical staining was applied to determine the levels of tyrosine hydroxylase and acetylcholine transferase （main markers of cardiac autonomic nerve distribution）. In addition, the correlation between cardiac autonomic nerve distribution and cardiac arrhythmia was investigated. RESULTS： Cardiac autonomic nerves were reported to exhibit a disordered distribution in different sites, mainly at the surface of the cardiac atrium and pulmonary vein, forming a ganglia plexus. The distribution of the pulmonary vein autonomic nerve was prominent at the proximal end rather than the distal end, at the upper left rather than the lower right, at the epicardial membrane rather than the endocardial membrane, at the left atrium rather than the right atrium, and at the posterior wall rather than the anterior wall. The main markers used for cardiac autonomic nerves were tyrosine hydroxylase and acetylcholine transferase. Protein gene product 9.5 was used to label the immunoreactive nerve distribution, and the distribution density of autonomic nerves was determined using a computer-aided morphometric analysis system. CONCLUSION： The uneven distribution of the cardiac autonomic nerves is the leading cause of the occurrence of arrhythmia, and the cardiac autonomic nerves play an important role in the occurrence, maintenance, and symptoms of arrhythmia.