OBJECTIVETo determine whether autoantibodies against the cardiac G-protein-coupled beta 2- and alpha 1-adrenergic and AT1 receptors are related to patients with primary hypertension.

METHODSSynthetic peptides corresponding to amino acid sequences of the second extracellular loops of the beta 2- and alpha 1-adrenergic and AT1 receptors were respectively used as antigens to screen sera from patients with hypertensive heart diseases (n = 50) as well as simple hypertension (n = 40) and healthy blood donors (n = 40) using ELISA test.

RESULTSThe positive ratio of autoantibodies against beta 2 and alpha 1 and AT1 receptors in patients with hypertensive heart diseases were significantly higher than patients with simple hypertension and healthy donors. The geometric mean titers of autoantibodies against beta 2- and alpha 1-adrenergic and AT1 receptors had no difference between the patients with hypertensive heart diseases and the patients with simple hypertension, but the geometric mean titers of two groups were higher than healthy donors. In the patients with hypertensive heart diseases, 81.0% of the patients with autoantibodies against beta 2-adrenergic receptor had autoantibodies against alpha 1-adrenergic receptor and 76.2% had autoantibodies against AT1 receptors. The percent of the autoantibodies against three receptors in patients with hypertensive heart diseases were 52.4%.

CONCLUSIONSAutoantibodies against beta 2- and alpha 1-adrenergic and AT1 receptors play an important role in the pathophysiological changes of primary hypertension, and may participate myocardial and vessel remodeling.

Adult ; Aged ; Autoantibodies ; blood ; Female ; Humans ; Hypertension ; immunology ; Male ; Middle Aged ; Receptor, Angiotensin, Type 1 ; immunology ; Receptors, Adrenergic, alpha-1 ; immunology ; Receptors, Adrenergic, beta-2 ; immunology

OBJECTIVETo elucidate the relationship between rat hepatic stellate cells (HSC) and sympathetic neurotransmitter norepinephrine (NE) during liver fibrosis.

METHODSUsing immunofluorescence and RT-PCR, the expressions of a1 and b2-adrenoceptors in activated HSC were detected. Methyl thiazolyl tetrazolium (MTT) was adopted to investigate the effect of NE on the proliferation of HSC. Meanwhile, the expressions of collagen-1, transforming growth factor beta (TGFb) and smooth muscle a-actin (a-SMA) in NE-stimulated HSC were detected by RT-PCR. The contents of NE in HSC were determined by high performance liquid chromatography-electrochemical detector (HPLC-ECD).

RESULTSThe a1 and b2-adrenoceptors were expressed in HSC. NE markedly stimulated the proliferation of HSC in a concentration-dependent manner (F = 140.464, P less than 0.05). NE induced the mRNA expressions of collagen-1, TGFb and a-SMA in HSC (t= -4.160; t= -8.763; t= -17.651, P less than 0.05). HSC were synthesizing and releasing NE, especially when stimulated with platelet-derived growth factor (PDGF) (10 ng/ml) (t= -32.907, P less than 0.05).

CONCLUSIONOur findings show that HSC are direct targets of NE and HSC are hepatic neuroglial cells that produce and respond to sympathetic neurotransmitter norepinephrine, suggesting that interrupting sympathetic nervous system signaling may be useful in the treatment of liver fibrosis.

Actins ; metabolism ; Animals ; Cell Proliferation ; drug effects ; Cells, Cultured ; Collagen Type I ; metabolism ; Hepatic Stellate Cells ; drug effects ; metabolism ; Liver Cirrhosis ; Norepinephrine ; pharmacology ; Rats ; Receptors, Adrenergic, alpha-1 ; metabolism ; Receptors, Adrenergic, beta-2 ; metabolism ; Transforming Growth Factor beta ; metabolism

OBJECTIVETo evaluate the effect of carvedilol on the cardiac function and autoantibodies against the cardiac beta(1), beta(2) and alpha(1)-adrenergic receptors in patients with chronic heart failure (CHF).

METHODS54 patients with CHF were divided randomly into two groups, one was regular treatment group treated with ACE inhibitor, digoxin and diuretic, another was carvedilol treatment group treated with carvedilol on the basis of above regular treatment. All the patients were followed up for six months and measured the changes of cardiac function and three autoantibodies by echocardiography and enzyme-linked immunosorbent assay (ELISA) respectively.

RESULTS(1) After carvedilol treatment, LVEDD and LVESD (57.50 +/- 7.29) mm and (43.17 +/- 8.27) mm were smaller than that in regular treatment group [(64.09 +/- 7.40) mm and (52.93 +/- 8.35) mm], and LVEF [(50.41 +/- 10.91)%] was higher than that [(41.70 +/- 7.45)%] in regular treatment group (P < 0.01). (2) After carvedilol treatment, the positive ratios and average titers of autoantibodies against the cardiac beta(1), beta(2) and alpha(1)-adrenergic receptors all decreased significantly compared with that of pre-treatment (P < 0.05). The positive ratios of autoantibodies against the three receptors in carvedilol treatment group were lower than those in regular treatment group (P < 0.05). The average titers of autoantibodies against the cardiac beta(1), beta(2) and alpha(1)-adrenergic receptors in carvedilol treatment group (1:72.44, 1:61.66 and 1:67.30) were lower than those in regular treatment group (1:113.24, 1:110.66 and 1:113.24), P < 0.05.

CONCLUSIONSCarvedilol decreased positive ratio and average titer of autoantibodies against the beta(1), beta(2) and alpha(1) receptors accompanied with the obvious improvement of cardiac function though the blockade of beta(1), beta(2) and alpha(1) receptors. It suggests that the autoantibodies might be involved in the process of pathophysiology and development of CHF. Carvedilol can inhibit this process.

Adult ; Aged ; Autoantibodies ; blood ; Carbazoles ; therapeutic use ; Female ; Follow-Up Studies ; Heart Failure ; drug therapy ; immunology ; physiopathology ; Humans ; Male ; Middle Aged ; Propanolamines ; therapeutic use ; Receptors, Adrenergic, alpha-1 ; immunology ; Receptors, Adrenergic, beta-1 ; immunology ; Receptors, Adrenergic, beta-2 ; immunology ; Young Adult

DNA was extracted from the peripheral venous blood of 338 subjects using BLOOD DNA MINI KIT. The 5 site SNP in 3 subtypes of Beta-AR were genotyped by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and allele-specific primer PCR techniques. The genotypes combination distribution of SNP at 5 sites in the 3 subtypes of Beta-AR were determined by clustering analysis technique. The natural combination distribution characteristics for SNP at 5 sites in the 3 subtypes of Beta-AR in 338 subjects were obtained. Sixty-seven combinations types were found. The preceding 5 combinations in the natural combination distribution of the SNP were: (1) The genotype combination of forty subjects was B1-AR S/S49+B1-AR R/R389+B2-AR R/G16+B2-AR Q/E27+B3-AR W/W64, its probability was 11.83%. (2) The genotype combination of thirty-three subjects was B1-AR S/S49+B1-AR R/R389+B2-AR R/G16+B2-AR Q/Q27+B3-AR W/W64, its probability was 9.76%. (3) The genotype combination of nineteen subjects was B1-AR S/S49+B1-AR R/G389+B2-AR R/G16+B2-AR Q/Q27+B3-AR W/W64, its probability was 5.62%. (4) The genotype combination of sixteen subjects was B1-AR S/S49+B1-AR R/G389+B2-AR R/G16+B2-AR Q/E27+B3-AR W/W64, its probability was 4.74%. (5) The genotype combination of thirteen subjects was B1-AR S/G49+B1-AR R/R389+B2-AR R/G16+B2-AR Q/E27+B3-AR W/W64, its probability was 3.85%. The obvious correlations exist among full sample and female or male subgroup, and between female and male subgroups.
Adult ; Aged ; Aged, 80 and over ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; methods ; Polymorphism, Single Nucleotide ; genetics ; Receptors, Adrenergic, beta ; classification ; genetics ; Receptors, Adrenergic, beta-1 ; genetics ; Receptors, Adrenergic, beta-2 ; genetics ; Receptors, Adrenergic, beta-3 ; genetics

OBJECTIVETo demonstrate the inhibitory effect of kappa-opioid receptor activation by U50488H on hypertrophy induced by NE in cultured neonatal rat cardiac myocytes and compare its effect with that of prazosin and propranolol.

METHODSThe cellular proliferation was determined with crystal violet staining. The protein content was assayed with Lowry's method. The cardiomyocytes volumes were measured by computer photograph analysis system. The protein synthesis was assayed with [3H]-lencine incorporation method.

RESULTS(1) NE significantly induced the increase of protein content, [3H]-leucine incorporation and cell size without a concomitant increase in cell number in low serum medium. OThese responses were partially suppressed by prazosin or propranolol alone and completely abolished by both in combination. U50488H significantly inhibited the NE-induced increase of protein content, [3H]-leucine incorporation and cell size. The inhibitory effects of U50488H on NE-induced cardiac hypertrophy were greater than either prazosin or propranolol, but comparable to combination of both.

CONCLUSIONNE, acting via both alpha1- and beta-adrenergic pathway, stimulates myocyte hypertrophy. Stimulating kappa-opioid receptor significantly inhibits NE-induced cardiac hypertrophy, which may be related with alpha1- and beta1-adrenergic pathway.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer ; pharmacology ; Adrenergic alpha-1 Receptor Antagonists ; pharmacology ; Adrenergic beta-Antagonists ; pharmacology ; Animals ; Animals, Newborn ; Cardiomegaly ; chemically induced ; pathology ; prevention & control ; Cell Enlargement ; drug effects ; Cells, Cultured ; Female ; Male ; Myocytes, Cardiac ; cytology ; Norepinephrine ; Prazosin ; pharmacology ; Propranolol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, kappa ; agonists

OBJECTIVETo investigate the alteration of expressions of beta(1)-, beta(2)-, beta(3)-adrenoceptor mRNA in human myocardial tissue and the relation between their expressions and cardiac function in patient with heart failure.

METHODSThe mRNA expressions of beta(1)-, beta(2)- and beta(3)-adrenergic receptors in myocardial tissue were analyzed by using the reverse transcriptase-polymerase chain reaction in 24 patients with heart failure of valvular heart disease and 5 control subjects.

RESULTSBeta(1)-adrenergic receptor mRNA expressions in myocardium were significantly lower in patients with heart failure than those in control subjects, and progressively reduced with aggravation of heart function. By contrast, beta(3)-adrenoceptor mRNA expressions were significantly higher in patients with heart failure than those in controls, and progressively elevated with aggravation of cardiac function. No difference was observed in beta(2)-adrenergic receptor among all groups.

CONCLUSIONThe changes of beta-adrenergic receptor mRNA expression are associated with the severity of heart failure.

Adult ; Case-Control Studies ; Female ; Heart Failure ; genetics ; metabolism ; physiopathology ; Humans ; Male ; Middle Aged ; RNA, Messenger ; metabolism ; Receptors, Adrenergic, beta-1 ; genetics ; metabolism ; Receptors, Adrenergic, beta-2 ; genetics ; metabolism ; Receptors, Adrenergic, beta-3 ; genetics ; metabolism

BACKGROUND: The effect of spinal adrenergic and cholinergic receptors on the anti-nociceptive effect of intrathecal ginsenosides was determined in a rat postoperative pain model. METHODS: Catheters were placed into the intrathecal space of male Sprague-Dawley rats. Postoperative pain was evoked by an incision to the plantar surface of a hind paw. Withdrawal thresholds was used as a nociceptive parameter and was measured with a von Frey filament. After observing the effect of intrathecal ginsenosides, an alpha-1 adrenergic receptor antagonist (prazosin), an alpha-2 adrenergic receptor antagonist (yohimbine), a muscarinic acetylcholine receptor antagonist (atropine), and a nicotinic acetylcholine receptor antagonist (mecamylamine) were given 10 min before administration of the ginsenosides to analyze the contribution of spinal adrenergic and cholinergic receptors on the antinociceptive effect of ginsenosides. RESULTS: Paw incision decreased withdrawal threshold in incised site of paw, but no change of withdrawal threshold was not seen in non-incised site. The intrathecal ginsenosides increased withdrawal threshold of the incised paw in a dose-dependent manner. Pre-treatment with both prazosin and intrathecal yohimbine antagonized the anti-nociceptive effect of the ginsenosides. However, pre-treatments with atropine or mecamylamine had any effect on the antinociceptive activity of ginsenosides. CONCLUSIONS: Intrathecal ginsenosides are effective in attenuation of postoperative pain induced in the rat model. Anti-nociceptive action of ginsenosides is partially mediated by spinal adrenergic receptors, but does not appear to be related to spinal cholinergic receptors.
Animals ; Atropine ; Catheters ; Ginsenosides ; Humans ; Male ; Mecamylamine ; Pain, Postoperative ; Prazosin ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic ; Receptors, Adrenergic, alpha-1 ; Receptors, Adrenergic, alpha-2 ; Receptors, Cholinergic ; Receptors, Muscarinic ; Receptors, Nicotinic ; Spinal Cord ; Yohimbine

OBJECTIVETo analyze the frequency distribution of single nucleotide polymorphisms (SNPs) of four asthma-related gene loci (ACE I/D; ADRB2 Arg16Gly; TNF-&alpha; G-308A; MS4A2 Glu237Gly) in 198 asthmatic children, and to investigate its association with genetic susceptibility to childhood asthma and some clinical phenotypes of asthma.

METHODSPolymerase chain reaction product electrophoresis identification and real-time quantitative PCR detecting system were used to determine the frequency distributions of the SNPs of the four asthma-related gene loci in 198 asthmatic children and 110 healthy controls. The serum total IgE (TIgE) levels and blood eosinophil proportion (%EOS) of the asthmatic children were measured. Different genotypes at the four asthma-related gene loci were compared in terms of TIgE and %EOS.

RESULTSThe genotype DD of angiotensin-converting enzyme (ACE) had a significantly higher frequency in the asthmatic children than in the healthy controls (χ2= 30.667, P<0.01), and the frequency of D allele was also significantly higher in the asthmatic children than in the healthy controls (χ2=7.151, P<0.01). No correlation was found between the polymorphism of each gene locus and serum TIgE level and %EOS (P>0.05).

CONCLUSIONSGenotype DD of ACE is related to genetic susceptibility to childhood asthma and may be the risk factor for childhood asthma.

Asthma ; etiology ; genetics ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Single Nucleotide ; Receptors, Adrenergic, beta-2 ; genetics ; Receptors, IgE ; genetics ; Tumor Necrosis Factor-alpha ; genetics

In the heart, stimulation of beta-adrenergic receptors (betaAR) serves as the most powerful means to increase cardiac contractility and relaxation in response to stress or a "fight-or-flight" situation. However, sustained beta-adrenergic stimulation promotes pathological cardiac remodeling such as myocyte hypertrophy, apoptosis and necrosis, thus contributing to the pathogenesis of chronic heart failure. Over the past decade, compelling evidence has demonstrated that coexisting cardiac betaAR subtypes, mainly beta(1)AR and beta (2)AR, activate markedly different signaling cascades. As a result, acute beta(1)AR stimulation activates the G(s) -adenylyl cyclase-cAMP-PKA signaling that can broadcast throughout the cell, whereas beta(2)AR-evoked cAMP signaling is spatially and functionally compartmentalized, due to concurrent G(i) activation. Chronic stimulation of beta(1)AR and beta(2)AR elicits opposing effects on the fate of cardiomyocytes: beta(1)AR induces hypertrophy and apoptosis; but beta(2)AR promotes cell survival. The cardiac protective effect of beta(2)AR is mediated by a signaling pathway sequentially involving G(i), G(betagamma), PI3K and Akt. Unexpectedly, beta(1)AR-induced myocyte hypertrophy and apoptosis are independent of the classic cAMP/PKA pathway, but require activation of Ca(2+)/calmodulin-dependent kinase II (CaMK II). The outcomes of cardiac-specific transgenic overexpression of either beta AR subtype in mice have reinforced the fundamentally different functional roles of these betaAR subtypes in governing cardiac remodeling and performance. These new insights regarding betaAR subtype stimulation not only provide clues as to cellular and molecular mechanisms underlying the beneficial effects of beta AR blockers in patients with chronic heart failure, but also delineate rationale for combining selective beta(1)AR blockade with moderate beta(2)AR activation as a potential novel therapy for the treatment of chronic heart failure.
Adenylyl Cyclases ; metabolism ; Animals ; Cyclic AMP-Dependent Protein Kinases ; metabolism ; GTP-Binding Proteins ; metabolism ; Heart ; physiology ; Heart Failure ; physiopathology ; Humans ; Myocardium ; metabolism ; Receptors, Adrenergic, beta ; classification ; physiology ; Receptors, Adrenergic, beta-1 ; physiology ; Receptors, Adrenergic, beta-2 ; physiology ; Signal Transduction

Recent reports suggest that the responses of the detrusor muscle to the hypogastric nerve stimulation and some autonomic drugs may not be identical among various species. In this study, the responses of the isolated detrusor muscle strips of the Amyda Japonica and the rabbit to catecholamines were compared, and the type of the adrenergic-receptors was investigated. The results obtained were as follows : 1. Catecholamines (norepinephrine and epinephrine) evoked only contraction in the isolated detrusor muscle of the Amyda Japonica and relaxation in the preparation of the rabbit. 2. The contraction-response in the Amyda Japonica was blocked in the presence of regitine, an adrenergic alpha-receptor blocking agent. 3. The relaxation-response in the rabbit was abolished by pre-treatment with propranolol, an adrenergic beta-receptor blocking agent. 4. Acetylcholine elicited contraction in both of the isolated detrusor muscle strips of the Amyda japonica and the rabbit, and the response was completely blocked in the presence of atropine. 5. The results described above suggest that catecholamines exert excitatory effect on the detrusor muscle of the Amyda japonica as it contains adrenergic alpha-receptors and inhibitory effect on the same preparation of the rabbit as it contains the adrenergic beta-receptors. Key Word : amyda japonica,alpha receptor, beta receptor.
Acetylcholine ; Atropine ; Autonomic Agents* ; Catecholamines ; Phentolamine ; Propranolol ; Receptors, Adrenergic, alpha ; Receptors, Adrenergic, beta ; Relaxation