Effects on electrical restitution of given esmolol during cardiopulmonary resuscitation in a swine ventricular fibrillation model / 中华急诊医学杂志

Objective To investigate the effect on electrical restitution of β1-adrenergic receptor antagonist esmolol administered during cardiopulmonary resuscitation in the porcine ventricular fibrillation model. Method Ventricular fibrillation untreated for four minutes was induced by dynamic steady state pacing protocol in 40 healthy male pigs, in which local unipolar electrograms were recorded using one 10-electrode catheter that was sutured to the left ventrieular epicarditan. During CPR, animals were randomized into two groups to receive saline as placebo or esmolol after two standards doses of epinephrine. At postresuscitation 2-hour, six pigs were randomly selected from each group and the second VF induction was performed. Local activation-recovery intervals (ARI) restitutions and the VF inducibility between control group and esmolol group were compared. Western blotting was performed to determine cardiac ryanodine receptor (RyR2) protein expression, and their phosphorylation status. Results No sig-nificant differences were observed at the restoration of spontaneous circulation between two groups. Higher postre-suseitation 2-hour survival rate was observed in the esmolol group. Esmolol significantly flattened ARI restitution slope, lessened regional difference of ARI restitution, decreased the VF inducibility, and alleviated RyR2 hyper-phosphorylation. Conclusions Esmolol given during CPR significantly improved postresuscitation 2-hour survival rate. Its effects on modulating electrical restitution property and intracellular calcium handling make up the most important reasons why β1-blockade significantly reduced the onset and maintenance of VF.

Infarto perioperatorio en cirugía no-cardíaca y dexmedetomidina / Perioperative myocardical infaction in non-cardiac surgery and dexmedetomidine

La patología cardiovascular es la primera causa de muerte en Chile y en el mundo. Desde el punto de vista quirúrgico, anestesiólogos y cirujanos enfrentan más frecuentemente pacientes mayores con patología cardiovascular. La incidencia de isquemia miocárdica en pacientes de alto riesgo, sometidos a cirugía no-cardíaca, es cercana al 40 por ciento durante el perioperatorio. La incidencia de infarto miocárdico y muerte en cirugía no-cardíaca, oscila entre 1 y 5 por ciento. Existe una estrecha relación entre los eventos isquémicos perioperatorios y el aumento de la morbimortalidad cardiovascular. Por este motivo, se han desarrollado medidas terapéuticas orientadas a disminuir la incidencia de isquemia perioperatoria y aminorar el daño asociado a ella. La adecuada identificación de pacientes de riesgo, la optimización del tratamiento médico de patologías asociadas y el uso de fármacos cardioprotectores durante el perioperatorio, han mostrado disminuir la incidencia de complicaciones cardíacas. Dexmedetomidina es un agonista beta2-adrenérgico de uso frecuente en anestesia. La evidencia sugiere que posee propiedades cardioprotectoras que podrían beneficiar a pacientes quirúrgicos de alto riesgo cardiovascular. La cardioprotección conferida por dexmedetomidina estaría mediada por la modulación del sistema nervioso autónomo. La disminución de la frecuencia cardíaca y de la presión arterial observada durante su uso, evitarían el desbalance entre aporte y demanda de oxígeno miocárdico y atenuarían el estrés sobre placas ateromatosas inestables. Hasta este momento se desconoce si dexmedetomidina produce precondicionamiento cardíaco y si activa vías transduccionales asociadas a cardioprotección. Frente a la actual realidad epidemiológica en Chile y el mundo, es importante estudiar y definir, cuales son los fármacos de uso frecuente en anestesia con capacidad cardloprotectora y los mecanismos Involucrados en esta protección. Sería Interesante lograr...

Cardiovascular disease is the leading cause of death In Chile and worldwide. Anesthesiologists and surgeons often face more elderly surgical patients with cardiovascular disease. The incidence of myocardial Ischemia in patents at high risk, undergoing non-cardiac surgery is about 40 percent during the perioperative period. The incidence of myocardial Infarction and death in non-cardiac surgery is between 1 and 5 percent. There is a close relationship between perioperative Ischemic events and increased cardiovascular morbidity and mortality Therefore, therapeutic approaches have been developed to reduce the Incidence of perioperative Ischemia and lessen the damage associated with it. The proper Identification of patients at risk, optimizing the medical treatment of associated diseases and the use of cardioprotective drugs during the perioperative period have shown to decrease the Incidence of cardiac complications. The beta2-adrenergic agonist dexmedetomidine is commonly used in anesthesia. The evidence suggests that possesses cardioprotective properties that could benefit surgical patients at high cardiovascular risk. The cardioprotection conferred by dexmedetomidine would be mediated by modulation of the autonomic nervous system. The decrease in heart rate and blood pressure observed during its use could avoid the Imbalance between supply and myocardial oxygen demand and lessen the stress on unstable athermanous plaques. So far it is unknown whether dexmedetomidine produces cardiac preconditioning by activating cardioprotective-signaling pathways. Faced with the current worldwide epidemiologic situation, It would be Important to study the cardioprotective capacity of drugs frequently used in anesthesia and the mechanisms Involved In that protection. It would be interesting to achieve that definition regarding the perioperative use of dexmedetomidine.

Effect of Korean Red Ginseng on Stress Responses and beta-Adrenergic Receptor Function in a Normal Population / 대한정신약물학회지

OBJECTIVE : There have been few studies to examine the effect of Korean red-ginseng on autonomic nervous system. The aim of this study is to examine the effect of Korean red-ginseng on beta-adrenergic receptor function in a normal population. METHODS : Thirty four healthy normal subjects who were 20-40 years old were recruited for the study. They were randomized into the two groups ; red-ginseng group (n=19) and placebo group (n=15). Three gram of red-ginseng or placebo per day was administered to the study subjects for 3 weeks. Before and after the medications, we measured the lymphocyte beta-adrenergic receptor function (Bmax, cAMP, and Kd), and psychological scales such as the Stress Response Inventory (SRI), Beck Depression Inventory (BDI), and Spielberger State and Trait Anxiety Inventory (STAI). This study was a double-blind, placebo-controlled, randomized, comparative study. RESULTS : There were no significant differences in the changes of beta-adrenergic receptor density (Bmax) and sensitivity (cAMP) and psychological assessments between the two groups according to the medications. However, we found significant (group x time) effects for Kd, and beta-adrenergic receptor affinity (1/Kd) was increased significantly in the Korean red-ginseng group. CONCLUSION : In a normal population, Korean red-ginseng showed a potential effects on the beta-adrenergic receptor function, which may play an important role in the regulation of stress responses

Effect of Korean Red Ginseng on Stress Responses and beta-Adrenergic Receptor Function in a Normal Population / 대한정신약물학회지

OBJECTIVE : There have been few studies to examine the effect of Korean red-ginseng on autonomic nervous system. The aim of this study is to examine the effect of Korean red-ginseng on beta-adrenergic receptor function in a normal population. METHODS : Thirty four healthy normal subjects who were 20-40 years old were recruited for the study. They were randomized into the two groups ; red-ginseng group (n=19) and placebo group (n=15). Three gram of red-ginseng or placebo per day was administered to the study subjects for 3 weeks. Before and after the medications, we measured the lymphocyte beta-adrenergic receptor function (Bmax, cAMP, and Kd), and psychological scales such as the Stress Response Inventory (SRI), Beck Depression Inventory (BDI), and Spielberger State and Trait Anxiety Inventory (STAI). This study was a double-blind, placebo-controlled, randomized, comparative study. RESULTS : There were no significant differences in the changes of beta-adrenergic receptor density (Bmax) and sensitivity (cAMP) and psychological assessments between the two groups according to the medications. However, we found significant (group x time) effects for Kd, and beta-adrenergic receptor affinity (1/Kd) was increased significantly in the Korean red-ginseng group. CONCLUSION : In a normal population, Korean red-ginseng showed a potential effects on the beta-adrenergic receptor function, which may play an important role in the regulation of stress responses

Alterations of beta-Adrenergic Receptor Signaling in Cardiac Hypertrophy and Heart Failure: beta-Adrenergic Receptor Desensitization in Cardiac Disease

beta-adrenergic receptors (betaAR) belong to the large family of G protein-coupled receptors that form the interface between the sympathetic nervous and cardiovascular systems. G protein-coupled receptors undergo adaptation to repeated or prolonged agonist stimulation, which is termed desensitization. Significant betaAR desensitization occurs with the development of cardiac hypertrophy and heart failure, and uncoupling of betaARs and defects in this pathway might be primary elements underlying the transition from compensated to uncompensated cardiac failure. Decreasing the level of myocardial betaARK1 in established heart failure is a novel approach to improving impaired betaAR receptor function, and potentially alter the pathogenesis of this disease.

Effect of carvedilol on mitochondrial respiratory function of pressure overload induced left ventricular hypertrophy in rats and its mechanism / 医学研究生学报

Objective: To understand the effect of Carvedilol on mitochondrial oxidative phosphorylation function during the development of pressure overload induced left ventricular hypertrophy in rats and its mechanism.Methods: Male SD rats were randomized into 6 groups: 5-and 15-week coarctation of the abdominal aorta(H5,H15),5-and 15-week Carvedilol intervention(HR5,HR15) and 5-and 15-week sham operation(S5,S15).Hemodynamics and ventricular remodeling parameters were measured,and the mitochondrial respiratory function was detected by Clark oxygen electrode.Results: Compared with S5,mitochondrial state 3 and 4 respiration and the oxidative phosphorylation rate(OPR) were increased and the respiratory control rate(RCR) decreased significantly in the H5 group.In comparison with S15,state 3 respiration,OPR and RCR were reduced significantly in the H15group.Carvedilol increased the three parameters and restored them to the level of the S15.Conclusion: Mitochondrial respiratory function decreased during the development of pressure overload induced left ventricular hypertrophy in rats.Carvedilol could protect mitochondrial respiratory function and improve myocardial energy metabolism,which might be a mechanism underlying its protective effect on myocardium.

Changes of beta-Adrenergic Receptor mRNA in the Visual Cortex and Superior Colliculus of Monocular Deprivated Rat

PURPOSE: To investigate the change of the Beta adrenergic system in the rat visual cortex and superior colliculus after visual deprivation during a critical period of postnatal development. METHODS: The changes of beta 1 and beta 2 adrenergic receptor mRNA were investigated by using northern blot analysis in the rat visual cortex and superior colliculus. The right eyelid of visually deprived rat was sutured at the 10th postnatal days. After visual deprivation for 4 weeks, the rat were sacrificed and the visual cortex and superior colliculus tissues were removed for analysis. RESULTS: Beta 1 and beta 2 adrenergic receptor mRNA expression was decreased in the contralateral visual cortex to the deprived eye. In the superior colliculus, beta 2 adrenergic receptor mRNA expression increased in both sides, but a much greater increase was shown in the ipsilateral superior colliculus than the contralateral side. CONCLUSIONS: These results suggests that visual deprivation during a critical period of postnatal development influences the beta adrenergic system in the rat visual cortex and superior colliculus.

Beta-adrenergic Receptor Function and Anxiety in Patients with Irritable Bowel Syndrome / 신경정신의학

OBJECTIVES: Recently, irritable bowel syndrome (IBS) is known to be related with neurotransmitters. This study was designed to determine beta-adrenergic receptor function in patients with IBS and to compared with normal controls to examine the relationship between beta-adrenergic receptor function and anxiety in IBS patients. METHODS: Eighteen IBS patients were compared with the same number of age and sex-matched normal subjects in terms of beta-adrenergic receptor function and psychological variables reflecting anxiety levels. To assess beta-adrenergic receptor function, Chronotropic 25 dose (CD25) was calculated via isoproterenol stimulation test. RESULTS: CD25 values in the patient group were significantly lower than those in the control group, which reflected increased beta-adrenergic receptor function (2.19+/-1.08 versus 3.89+/-1.64, p<0.05). Patients with IBS showed higher HAM-A scores (8.88+/-4.88 versus 3.59+/-2.65, p<0.01), HAM-D scores (6.41+/-4.02 versus 2.47+/-2.40, p<0.01), BDI scores (9.00+/-6.21 versus 4.72+/-4.30, p<0.05), and STAI scores (STAI-S: 43.41+/-6.34 versus 33.83+/-8.18, p<0.01, STAI-T: 44.65+/-7.43 versus 38.17+/-8.45, p<0.05). In addition, HAM-A scores were negatively correlated with CD25 values in the patient group (r=-0.424, p<0.01). CONCLUSION: These results suggest that beta-adrenergic receptor function is increased in patients with IBS, which could affect increased anxiety levels in these patients.

Milnacipran versus Sertraline in Major Depressive Disorder: A Double-Blind Randomized Comparative Study on the Treatment Effect and cbeta-Adrenergic Receptor Responsiveness / 대한정신약물학회지

OBJECTIVE: This study was aimed to compare the efficacy and tolerability of milnacipran and sertraline treatment in patients with major depressive disorder and to evaluate the relationships between beta-adrenergic receptor responsiveness and depressive mood states. METHODS: Fifty three patients who had a diagnosis of major depressive disorder according to the DSM-IV and showed scores of 17 or more on the 17-item Hamilton Rating Scale for Depression (HAM-D) were randomly assigned to either milnacipran or sertraline treatment group. Each patient received 8 weeks of antidepressant treatment with one of the two drugs. Efficacy was assessed using the HAM-D, Beck Depression Inventory (BDI), Montgomery and Asberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI). Twenty normal control subjects who had no history of psychiatric and major medical illness and were matched with the depressed patients considering age, sex and body mass index were recruited for the comparison of beta-adrenergic receptor responsiveness between depressed patients and normal control subjects. We measured beta-adrenergic receptor density, lymphocyte cAMP ratio (ratio of isoproterenol-stimulated cAMP/basal cAMP), and receptor affinity (Kd) in all subjects. We also investigated beta-adrenergic receptor responsiveness before and after treatment in depressed patients. RESULTS: Twelve patients in milnacipran group and 15 patients in sertraline group were completed this study. In all assessment scales for depression, we found significant decrease in depression severity in both milnacipran and sertraline groups. Both of the two drugs proved equally effective for reduction of the overall symptoms of depression throughout the treatment period. And there were significant differences in the means of Kd values between control subjects and depressed patients before treatment. We found a significant negative correlation between Kd values and BDI scores. After treatment with either milnacipran or sertraline, cAMP ratio (4.8+/-1.6 vs 5.7+/-2.5, p=0.095) and Kd value (65.6+/-11.9 vs 74.6+/-7.8, p=0.066) tended to increase, but there was no significant difference in beta-adrenergic receptor responsiveness between milnacipran and sertraline group. CONCLUSION: Both milnacipran and sertraline were not different in the clinical efficacy in major depressive disorder. In depressed patients, beta-adrenergic receptor responsiveness is reduced and both milnacipran and sertraline antidepressants tended to increase beta-adrenergic receptor responsiveness.

The Effect of Antidepressant Treatment on Beta-Adrenergic Receptor Responsiveness in Patients with Major Depression / 대한정신약물학회지

Many studies have reported reduced beta-adrenergic receptor responsiveness in major depression, but there were few studies to see the effect of antidepressant treatment on beta-adrenergic receptor function in depressed patients. This study examined beta-adrenergic receptor responsiveness in patients with major depression before and after antidepressant treatment. After careful psychiatric interviews by two experienced psychiatrists, twenty depressed patients (Hamilton Depression Rating Scale scores>18) were randomly assigned to 8 weeks of double-blind treatment with either milnacipran or sertraline. Twenty normal control subjects who had no previous history of major medical and psychiatric illness were matched with the patients considering age, sex and body mass index. The Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A) were performed to assess clinical change of depression in the patients before and after treatment. We measured the lymphocyte cyclic AMP ratio (ratio of isoproterenol-stimulated cAMP/ basal cAMP), beta-adrenergic receptor density (Bmax) and receptor affinity (Kd) in all subjects. Depressed patients showed much lower HAM-D scores (25.7+/-4.8 vs. 14.3+/-9.1, p=0.002), MADRS scores (34.3+/-5.7 vs. 21.5+/-13.1, p=0.005) and HAM-A scores (31.4+/-7.9 vs. 22.1+/-13.5, p=0.040) after 8 weeks of antidepressant treatment than those before treatment. There were statistically significant differences in the means of Bmax and Kd between control subjects and patients before treatment. Contrary to our expectation, there was no statistically significant difference in the means of cAMP ratio between the two groups. Lymphocyte Bmax (4.90+/-3.08 vs. 8.13+/-3.08, p=0.027) and Kd (63.61+/-6.52 vs. 70.89+/-9.40, p=0.029) in the patients increased after antidepressant treatment. This result suggests that antidepressant treatment increases beta-adrenergic receptor responsiveness in depressed patients.

Association between betaARK1 Level of Circulating Mononuclear Leukocytes and Left Ventrcular mass in Non-treated Hypertensive Patients

BACKGROUND: Beta-adrenergic receptor Kinase 1(betaARK1) is a serine/threonine kinase attached, which inhibits the coupling of beta-adrenergic receptor with G-protein. Myocardial betaARK1 level is usually elevated in heart failure and hypertrophy, but it is not known whether the circulating betaARK1 level is related with the degree of cardiac hypertrophy. This study was performed to evaluate the association of the betaARK1 level in circulating mononuclear leukocytes(MNL) in untreated hypertension with left ventricular mass in hypertensive patients. Method: Nineteen non-treated hypertensive patients were included for this study. High blood pressure was confirmed when systolic BP is over 150 mmHg or diastoli BP is over 95 mmHg. Echocardiography was performed to evaluate the degree of hypertrophy by measuring the left ventricular mass index(LVMI) and relative wall thickness(RWT), and test the LV function by measuring the ejection fraction(EF) according to ASE guideline. At the same time, blood was collected from each patient and MNL were isolated by gradient centrifuge with Ficoll-400. Total RNA was purified from MNL and semi-quantitative RT-PCR was performed. After reverse transcription, PCR was done with primers for human betaARK1 and GAPDH as external control. betaARK1 levels were expressed by ratio to GAPDH level and estimated the relations with clinical and Echocardiographic parameters. Result: We studied confirmed 19 hypertensive patients(10 men and 9 women, mean age of 50.6 years). Echocardiographically measured indices(mean+/-SD) were as follows; LVMI(137.3+/-30.6g/m2), PWT(0.53+/-0.09) and EF(54.6+/-8.5%). Ratio of betaARK1 levels to GAPDH was from 0.10 to 0.96 (0.62+/-0.25). betaARK1 levels were correlated with LVMI(correlation coefficient: r=.502, p=.029) and RWT(r=.627, p=.004). But Systolic BP(r=0.009, p=.93), diastolic BP(r=.07, p=.85) or EF(r=.045, p=.84) were not related to level of betaARK1. CONCLUSIONS: The betaARK1 level of circulating MNL was correlated well with the degree of the cardiac hypertrophy estimated by LVMI and RWT. This data suggests that activation of sympatho-adrenal system would exert a major role in developing cardiac hypertrophy and we can expect the decreased responsiveness to catecholamine in the heart of hypertensive patients. betaARK1 in circulating MNL might be used as a predictor or marker for LV hypertrophy in hypertensive patients.

Relaxing Effects of Isoproterenol and Nitric oxide on the Contractile responses of the Rat Bladder Muscle Strip

No abstract available.

Neural adaptation of beta adrenergic receptor subtypes after chronic imipramine treatment: A quantitative autoradiographic study

This study compares the subtypes of central beta adrenergic receptors (ARs) of brains of untreated rats with those of imipramine-treated rats. Beta adrenergic receptors were measured by quantitative autoradiography of the binding of 3H-dihydroalprenolol (3H-DHA) in coronal sections of rat brain. Repeated treatment of rats with imipramine significantly reduced the binding of 3H-DHA to beta-1 AR in many brain areas, especially throughout the cerebral cortex, hippocampus, thalamus, and amygdala. Significant reductions of the binding of 3H-DHA to beta-2 AR were not found in any area of the brain. These data suggests that a selective down-regulation of beta-1 AR may be involved in the adaptive changes occurring after prolonged imipramine treatment.

Expression and Distribution of Beta 2 Adrenergic Receptor mRNA in the Rat eye

Beta adrenergic receptors(beta-ARs) were detected in retina, trabecular meshwork, iris and ciliary body in eye of human, cat, rabbit, and bovine using in vitro autoradiography and majority of the beta-ARs found in eye are the beta2 subtype. Recently, the beta2-AR gene has been cloned from hamster, human, rat and monkey using molecular biological methods. Expression of beta2-AR mRNA were demonstrated in smooth muscle, kidney, ovary, brain, adipose tissue, heart, epithelial cells, thymus, lung and liver. However, studies about expression and distribution of beta2-AR mRNA in the eye have not been done yet. Author have characterized the expression of beta2-AR mRNA in rat eye using in situ hybridization with 35S-UTP riboprobe. beta2-AR mRNA was expressed in corneal epithelium and stroma, ciliary epithelium, vessels of ciliary body, choroidal vessel, and retina. In contrast it was not expressed in iris and sclera in the rat eyes. These results support the hypothesis that beta2-AR mRNA may be synthesized in the various ocular tissue and its characterized distribution suggests partially that beta2-ARs are related with aqueous production and blood supply of the eye.

Phorbol Esters Attenuate The Action of Isoproterenol on Vascular Smooth Muscle

The effects of phorbol esters were studied in rabbit carotid artery to evaluate the action of protein kinase C on the regulation of vascular tone by isoproterenol. The vascular rings, 2 mm in width, were myographied isometrically in an isolated organ bath and the effects of phorbol 12,13-dibutyrate(PDBu) and phorbol 12-myristate 13-acetate(PMA) were determined. Isoproterenol, a beta adrenergic agonist, relaxed the vessel which was precontracted by phenylephrine, but not that by phorbol esters. The action of isoproterenol was attenuated by removal of endothelium or pretreatment with methylene blue or nitro-L-arginine. The pretreatment with phorbol esters at concentrations which did not induce contraction, decreased isoproterenol-induced relaxation of vascular rings with or without endothelium. The action of PDBu on isoproterenol-induced relaxation was less effective than that of PMA, unlike those observed in contractile response, but the contractile effect of the former was more potent than that of the latter. PMA did not affect relaxant effect of forskolin, an activator of adenyl cyclase. Staurosporine, a protein kinase C inhibitor, inhibited the action of these drugs on both isoproterenol-induced relaxation and the contractile response. These results suggest that the relaxation induced by isoproterenol was reducd by the activation of protein kinase C, which may be isozyme different from that involved in contractile response.

Effect of Propranolol on Changes in Sereum K+ Induced by brachial Plexus Block / 대한마취과학회지

When we perform the regional blockade, we usually addit epinephrine to the local anesthetics for the purpose of lengthening anesthesia time and preventing the systemic reaction of local anesthetics. In that situation, epinephrine produces decrease in serum potassium concentration and changes in electrocardiogram. We investigated the influence of propranolol on changes in serum potassium and ECG induced by brachial plexus block with 30ml of mixture of local anesthetic (2% lidocaine +0.5% bupivacaine) which contains 1:200,000 epinephrine. The subjects classified as following two groups: Group l : Brachial plexus block with mixture of local anesthetic and 1:200,000 epinephrine(n=20). Group ll : Pretreated with 2 mg of propranolol(slow intravenous injection for 5 min. before block) and performed as Group l. The results were as follows: 1) Group l showed statistically significant decrease of serum potassium after 10, 20, 30 min. of block(p<0.05). Group ll did not show any significant change. 2) Group l showed progressive flattening of T wave and appearance of U wave (25% of pts) in ECG as the serum-potassium decreased progressively, but Group ll did not sho any significant change. 3) The epinephrine mediated beta-adrenergic stimulation may be considered as the cause of epinephrine induced hypokalemia during brachial plexus block.

The beta-adrenergic Receptor Concentration and Plasma Catecholamine in Congestive Heart Failure

To identify the role of the myocardial beta-adrenergic pathway in congestive heart failure, we examined beta-adrenergic receptor density and C-AMP by receptor assay with mononuclrear cell and polymorphonuclear cell in 7 cases of normal control and 7 cases of congestive heart failure. The results were as follows: 1)The mean serum concerntrations of norepinephrine(566.00+/-48.12 pg/ml)and epinephrine(353.14+/-44.24 pg/ml) in congestive heart failure group were significantly higher than those(218.12+/-17.08 pg/ml, 187.23+/-24.62 pg/ml)in normal contral group(P<0.05 for each comparison). 2) In normal control group, the receptor concentration of mononuclear cell was 35.51+/-19.19 fmol/mg and that of polymorphonuclrear cell was 35.53+/-15.05 fmol/mg. The affinity constant of mononuclear cell was(2.47+/-0.42)x10(9)/m and that of polymorphonuclear cell was(2.24+/-0.58)x10(9)/m. 3) In congestive heart failure group, the receptor concentration of mononuclear cell(29.31+/-5.41 fmol/mg) was significantly lower than that in normal control group(p<0.05). And the affinity constant(3.57+/-1.02)x10(9)/m) was significantly higher than that in normal control group(p<0.05). 4) In congestive heart failue group, the receptor concentration of polymorphonuclear cell(33.15+/-10.46 fmol/mg) was not significantly different from that in normal control group. And the affinity constant(2.66+/-0.43)x109/m) was not significantly different from that in normal control group. 5) In congestive heart failure group, the C-AMP concentrations of mononuclear cell(basal 119.9+/-17.2 pmol/min/mg, isoproterenol stimulation 137.2+/-23.2 pmol/min/mg) were significantly lower than those(basal 205.2+/-21.1 pmol/min/mg, isoproterenol stimulation 267.5+/-34.3 pmol/min/mg) in normal control group(p<0.05 for each comparison). 6) In congestive heart failure group, the C-AMP concentrations of polymorphonuclear cell(basal 115.2+/-34.3 pmol/min/mg, isoproterenol stimulation 142.5+/-20.5 pmol/min/mg) were significantly lower thatn those(basal 186.3+/-24.2 pmol/min/mg, isoproterenol stimulation 233.4+/-32.2 pmol/min/mg) in normal control group(P<0.05 for each comparison). In conclusion, a decrease in beta-adrenergic density in congestive heart failure leads to subsensitivity of the beta-adrenergic pathway and decreased beta-agonist-stimulated contraction. However, other factors may be important in adenylate cyclase activation, and so further research is needed.

The effect of tranilast on the down-regulation of beta-adrenoceptors / 中国药理学通报

The effect of tranilast on the down- regulation of beta- adrenoceptor agonist was investigated. Male guinea pigs were divided into 3 groups, one group is control. Others were received injection of terbutaline or terbutaline plus tranilast for successive 5 days. The radioli-gand binding assays for beta-adrenoceptors in the lung membranes of the guinea pigs were per-formed. The results showed the numbers of maximal binding sites (Bmax) of beta-adrenoceptors in terbutaline group was significantly less than that in control group ( P 0. 05).The affinity ( Kd) of beta-adrenoceptors both in terbutaline group and in terbutaline plus tranilast group was higher than that in control (P

Changes of Beta-adrenergic Receptors and cAMP-PDE Activity of Asthmatic Lung Tissue in Guinea Pigs / 第三军医大学学报

The changes of the number of beta-adrenergic receptors, the activity of cAMP-PDE and the level of cAMP were observed in the guinea pigs with allergic asthma with radioligand assay, radioenzyme assay and radioimu-noassay respectively. It was found that there were a 25% decrease of the number of beta-adrenergic receptors on the lung membrane, a 36% decrease of the level of cAMP in the lung tissue, and a 35% increase of cAMP-PDE activity in the asthmatic animals as compared with those of the control. A close positive correlation was observed between the number of beta-adrenergic receptors and cAMP level,but a negative correlation between cAMP-PDE activity and cAMP level in the asthmatic group.