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OBJECTIVE To explore the effects of ADRB1 Arg389Gly polymorphisms on the efficacy of bisoprolol， thus providing some information for individualized drug therapy. METHODS A systematic search was conducted in PubMed， Embase， Cochrane Library， CBM， CNKI， and Wanfang Data to retrieve and find out all relevant literature about bisoprolol and ADRB1 Arg389Gly polymorphism from the inception to May 2023. The retrieved literature was screened and selected according to the inclusive and exclusive criteria， thereafter quality assessment was conducted. RevMan 5.4 software was utilized to perform the meta- analysis for the outcome index. RESULTS Overall 7 literature with 1 339 cases were included. Among them， 4 studies provided the changes in systolic blood pressure （SBP）， diastolic blood pressure （DBP） （ΔSBP and ΔDBP）； 4 involving the change （ΔLVEF） of left ventricular ejection fraction （LVEF）. Results of the study showed that there was no statistical significance in the improvement of blood pressure between wild-type group （AA） and mutation group （AG+GG） of ADRB1 Arg389Gly treated with bisoprolol {ΔSBP [SMD＝0.17，95%CI （－0.97，1.31）， P＝0.77]， ΔDBP [SMD＝－0.01，95%CI （－0.65，0.62）， P＝0.97]}； there was no statistical significance in the improvement of ΔLVEF [SMD＝－0.61， 95%CI （－2.74，1.53）， P＝0.58] between 2 groups. CONCLUSIONS ADRB1 Arg389Gly gene polymorphism has no significant influence on the improvement of SBP， DBP， and LVEF in cardiovascular patients who use bisoprolol.
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Objective:To observe whether α1 adrenergic receptor (α1AR) blocker can reduce and antagonize portal hypertension caused by α1AR activation in rats, and to provide a new approach for the clinical treatment of portal hypertension.Methods:Phenylephrine was chosen as α1AR agonist, and alfuzosin was used as α1AR blocker. The route of administration was portal vein injection, and the pressure was measured by trans-portal vein puncture. According to random number table, 32 male Sprague-Dawley rats were divided into 4 groups: control group, portal hypertension model group, alfuzosin treatment group and alfuzosin prevention group. The portal venous pressure (PVP) was measured in all rats before administration. The rats in the control group were injected with 0.9% sodium chloride solution (1 L/g), and the rats in portal hypertension model group were injected with phenylephrine(1.5 μg/g), and the PVP of the above two groups was measured again at 5 and 10 min after injection. The rats in alfuzosin treatment group were injected with phenylephrine(1.5 μg/g), PVP was measured again at 5 min after administration, and then the rats were given alfuzosin(0.9 μg/g), PVP was measured again at 5 min after administration. The rats in alfuzosin prevention group were injected with alfuzosin(0.9 μg/g), PVP was measured at 1 min after administration, and then the rats were given phenylephrine(1.5 μg/g), PVP was measured again at 1, 5 and 10 min after phenylephrine injection respectively. One way analysis of variance and Dunnett- t test were used for statistical analysis. Results:The portal vein puncture was successfully performed in 4, 6, 8 and 5 rats in the control group, portal hypertension model group, alfuzosin treatment group and alfuzosin prevention group, respectively. The PVP of rats in portal hypertension model group at 5 and 10 min after phenylephrine injection was (18.045±7.636) and (15.515±5.440) mmHg (1 mmHg = 0.133 kPa), respectively, which were both higher than that before administration ((8.452±2.830) mmHg), and the differences were statistically significant ( t=2.89 and 2.82, both P<0.05). At 5 min after alfuzosin injection, the PVP of rats in the alfuzosin treatment group was (10.088±3.743) mmHg, which was lower than that of rats at 5 min after phenylephrine injection ((16.146±4.324) mmHg) and that of portal hypertension model group at 10 min after phenylephrine injection, and the differences were statistically significant ( t=3.00 and 2.22, both P<0.05). There were no significant differences in PVP in the alfuzosin prevention group before administration, at 1 min after injection of alfuzosin, and at 1, 5 and 10 min after injection of phenylephrine (all P > 0.05). Conclusions:α1AR is an important factor involved in the regulation of PVP, and its blockers can reduce and antagonize the portal hypertension caused by α1AR activation, which is of great significance in the prevention and treatment of portal hypertension progression in liver cirrhosis.
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Kidney is one of the important organs of the body.With both excretory and endocrine functions,it plays a vital role in regulating the normal physiological state.As a precursor of the nitric oxide(NO)synthesis
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Animals , Rats , Arginine/physiology , Kidney/physiology , Muscle, Smooth, Vascular , Nitric Oxide/physiology , Receptors, Adrenergic, alpha-1/physiology , Renal Insufficiency/physiopathology , Signal Transduction , VasoconstrictionABSTRACT
Objective To investigate whether endogenous nociceptin/orphanin FQ (N/OFQ) can inhibit arrhythmia and expression of β1-adrenergic receptor (β1-AR) on the surface of myocardial cell membrane in acute myocardial ischemia rats by Raf kinase inhibitory protein (RKIP). Methods ① Experiment one: according to random number table method, 30 adult male Sprague-Dawley (SD) rats with only 6 weeks of age were divided into Sham group (open the chest but do not ligate the coronary artery), myocardial ischemia model group (coronary ligation of left anterior descending branch), and endogenous N/OFQ antagonists UFP-101 pretreatment group (UFP-101 group, preoperative 10 minutes after tail vein injection of 1 mL/kg UFP-101), with 10 rats in each group. Arrhythmia was recorded within 15 minutes after operation. The expression of phosphorylated RKIP (p-RKIP) was detected by Western Blot. ② Experiment two: according to the random number table method, 304-week-old male SD rats were divided into UFP-101 control group, RKIP over expression group and RKIP antagonism group, with 10 rats in each group. The UFP-101 control group was intraperiton eally injected with corn oil every day, while the other two groups were injected with up adjuster of RKIP (Didymin). The rats in the three groups were all ligated after 4 weeks of feeding, and UFP-101 was injected through the tail vein 10 minutes before the operation. The RKIP antagonist group received intraperitoneal injection of the RKIP-specific antagonist locostatin 2 hours before surgery. Arrhythmia results were recorded within 15 minutes after operation. Western Blot was used to detect the expression of p-RKIP in myocardial tissue and expression of β1-AR on the surface of myocardial cell membrane 15 minutes after surgery. Results ①Experiment one: compared with Sham group, ventricular ectopic beat (VEB), ventricular tachycardia (VT) and ventricular fibrillation (VF) increased significantly in the model group and UFP-101 group, and arrhythmia score increased significantly. In addition, compared with the Sham group, p-RKIP expression was increased in the model group and decreased in the UFP-101 group. Compared with the model group, preconditioning with UFP-101 significantly reduced the occurrence of arrhythmia [arrhythmia score: 1.5 (0.3, 5.0) vs. 4.0 (2.0, 5.0), P < 0.05], and the expression of p-RKIP in myocardial tissue significantly decreased (p-RKIP/total RKIP: 0.20±0.11 vs. 0.43±0.11, P < 0.05). This indicated that antagonistic N/OFQ could reduce the phosphorylation of RKIP and the occurrence of arrhythmia. ② Experiment two:compared with the UFP-101 control group, overexpression of RKIP significantly increased the occurrence of arrhythmia events, and the expression of β1-AR on the surface of the myocardial cell membrane significantly increased. And antagonism RKIP overexpression could make the occurrence of arrhythmia eased [arrhythmia score: 3.0 (2.0, 3.0) vs. 4.0 (2.0, 5.0), P < 0.05], and significantly reduce the expression of myocardial cell membrane surface β1-AR (β1-AR/Na+-K+-ATPase: 0.88±0.09 vs. 1.02±0.08, P < 0.05), while there was no significant difference in total RKIP expression (total RKIP/GAPDH: 5.40±0.21 vs. 5.36±0.19, P > 0.05). This indicated that endogenous N/OFQ affected the expression of plasma β1-AR on the surface of myocardial cell membrane and ischemic arrhythmia in rats through RKIP. Conclusion Endogenous N/OFQ can affect the expression of plasma β1-AR on the membrane surface of ischemic myocardium and arrhythmia in rats via increased expression of RKIP phosphorylation.
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Objective@#To investigate whether endogenous nociceptin/orphanin FQ (N/OFQ) can inhibit arrhythmia and expression of β1-adrenergic receptor (β1-AR) on the surface of myocardial cell membrane in acute myocardial ischemia rats by Raf kinase inhibitory protein (RKIP).@*Methods@#① Experiment one: according to random number table method, 30 adult male Sprague-Dawley (SD) rats with only 6 weeks of age were divided into Sham group (open the chest but do not ligate the coronary artery), myocardial ischemia model group (coronary ligation of left anterior descending branch), and endogenous N/OFQ antagonists UFP-101 pretreatment group (UFP-101 group, preoperative 10 minutes after tail vein injection of 1 mL/kg UFP-101), with 10 rats in each group. Arrhythmia was recorded within 15 minutes after operation. The expression of phosphorylated RKIP (p-RKIP) was detected by Western Blot. ② Experiment two: according to the random number table method, 30 4-week-old male SD rats were divided into UFP-101 control group, RKIP over expression group and RKIP antagonism group, with 10 rats in each group. The UFP-101 control group was intraperiton eally injected with corn oil every day, while the other two groups were injected with up adjuster of RKIP (Didymin). The rats in the three groups were all ligated after 4 weeks of feeding, and UFP-101 was injected through the tail vein 10 minutes before the operation. The RKIP antagonist group received intraperitoneal injection of the RKIP-specific antagonist locostatin 2 hours before surgery. Arrhythmia results were recorded within 15 minutes after operation. Western Blot was used to detect the expression of p-RKIP in myocardial tissue and expression of β1-AR on the surface of myocardial cell membrane 15 minutes after surgery.@*Results@#①Experiment one: compared with Sham group, ventricular ectopic beat (VEB), ventricular tachycardia (VT) and ventricular fibrillation (VF) increased significantly in the model group and UFP-101 group, and arrhythmia score increased significantly. In addition, compared with the Sham group, p-RKIP expression was increased in the model group and decreased in the UFP-101 group. Compared with the model group, preconditioning with UFP-101 significantly reduced the occurrence of arrhythmia [arrhythmia score: 1.5 (0.3, 5.0) vs. 4.0 (2.0, 5.0), P < 0.05], and the expression of p-RKIP in myocardial tissue significantly decreased (p-RKIP/total RKIP: 0.20±0.11 vs. 0.43±0.11, P < 0.05). This indicated that antagonistic N/OFQ could reduce the phosphorylation of RKIP and the occurrence of arrhythmia. ② Experiment two: compared with the UFP-101 control group, overexpression of RKIP significantly increased the occurrence of arrhythmia events, and the expression of β1-AR on the surface of the myocardial cell membrane significantly increased. And antagonism RKIP overexpression could make the occurrence of arrhythmia eased [arrhythmia score: 3.0 (2.0, 3.0) vs. 4.0 (2.0, 5.0), P < 0.05], and significantly reduce the expression of myocardial cell membrane surface β1-AR (β1-AR/Na+-K+-ATPase: 0.88±0.09 vs. 1.02±0.08, P < 0.05), while there was no significant difference in total RKIP expression (total RKIP/GAPDH: 5.40±0.21 vs. 5.36±0.19, P > 0.05). This indicated that endogenous N/OFQ affected the expression of plasma β1-AR on the surface of myocardial cell membrane and ischemic arrhythmia in rats through RKIP.@*Conclusion@#Endogenous N/OFQ can affect the expression of plasma β1-AR on the membrane surface of ischemic myocardium and arrhythmia in rats via increased expression of RKIP phosphorylation.
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AIM:To investigate the relationship between adrenergic receptor(AR) R389G gene polymorphism and changes in intraocular pressure in patients with primary open angle glaucoma (POAG). METHODS: We selected 100 patients with newly diagnosed POAG from January 2015 to February 2017 in our hospital. The patient's intraocular pressure was measured at 6:00, 12:00, 18:00, and 24:00 daily and the mean value was calculated. Patients with mean intraocular pressure >30mmHg were included in Group A (44 patients), patients with mean intraocular pressure <30mmHg were treated as Group B (56 patients). The clinical data of two groups of patients were compared, and multivariate Logistic regression analysis was used to investigate the relationship between β1AR R389G gene polymorphism and changes in intraocular pressure in patients with POAG. RESULTS: The frequency of GG genotype in Group A (27.3%) was significantly higher than that in Group B (8 9%) (P < 0. 05). The allele G frequency was significantly higher in Group A (40.9%) than in Group B (18.8%), with a statistically significant difference (P<0 05). By multivariate Logistic regression analysis, increased systolic blood pressure and increased frequency of β1AR R389G allele were independent risk factors for increased intraocular pressure in POAG patients (P <0 05). CONCLUSION: The β1AR R389G gene polymorphism is closely related to POAG and is an independent risk factor for increased intraocular pressure in patients with POAG.
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Objective To investigate the effect of β1-Adrenoceptor autoantibody on liver function.Methods The biologically active of β1-AA was prepared and passive immunization model was established with β1-AA.The bio-chemical parameters of the liver were measured by the automatic serum biochemical analyzer.The liver size, hepatic vein,portal vein velocity were detected by liver ultrasound;hepatocytes apoptosis were tested by tunel stai-ning,annexin V/PI staining and caspase 3 activity detection.Results The biologically active of β1-AA and passive immunization model were established successfully.The ALT and AST of the liver significantly increased and the ALB decreased in the passive immunization process.The apoptosis of the hepatocytes increased,and meto-prolol partially reversed this effect.Conclusions β1-AA may induce hepatocytes apoptosis by β1-adrenergic receptor and participate in the development of liver injury.
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<p><b>PURPOSE</b>Renal denervation (RD) has been demonstrated to be an effective approach to reduce blood pressure for those with resistant hypertension. Yet, we aimed to explore the effect and possible mechanism of RD on blood-pressure response to hemorrhagic shock in spontaneously hypertensive rats.</p><p><b>METHODS</b>A total of 48 male spontaneously hypertensive rats were randomized to three groups: study group, sham-operation group and control group. RD was achieved by cutting off renal nerves and swabbing phenol on it. Ten weeks after RD, 8 rats in each group were sacrificed to collect the kidney and heart tissues. The remaining rats were subjected to an operation to induce hemorrhagic shock which would lead to 40% loss of total blood volume, and observed for 120 min. The serum concentration of norepinephrine was measured before and three weeks after RD.</p><p><b>RESULTS</b>The blood-pressure and norepinephrine levels were reduced significantly after RD (p < 0.05). Systolic blood pressure and diastolic blood pressure of the surgery group were higher than those in the sham and control groups at 15, 30 and 45 min after hemorrhagic shock (p < 0.05), while no significant difference was observed at 60, 90 and 120 min (p > 0.05). Additionally, the beta-1 adrenergic receptor (β1-AR) in the study group was significantly higher than those in the other two groups (p < 0.05) after hemorrhagic shock.</p><p><b>CONCLUSION</b>This study demonstrated that RD could to some extent improve blood-pressure response to hemorrhagic shock in an established model of severe hemorrhagic shock in spontaneously hypertensive rats. The mechanism might be associated with up-regulation of β1-AR.</p>
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OBJECTIVE@#To investigate the relationship between the levels of plasma adrenaline and norepinephrine and gene polymorphism of β1 adrenergic receptor G1165C 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 G1165C 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); There was no significant difference in the distribution of β1 adrenergic receptor G1165C 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 β1 adrenergic receptor G1165C have no significant correlation, not only with the susceptibility and severity of EV71 infection in hand, foot and mouth disease, but also with the levels of catecholamine.
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Objective To investigate the relationship between the levels of plasma adrenaline and norepinephrine and gene polymorphism of β1 adrenergic receptor G1165C 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 G1165C 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); There was no significant difference in the distribution of β1 adrenergic receptor G1165C 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 β1 adrenergic receptor G1165C have no significant correlation, not only with the susceptibility and severity of EV71 infection in hand, foot and mouth disease, but also with the levels of catecholamine.
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Objective To investigate the effect of selectiveα1 adrenergic receptor blocking agent in the treatment of bladder neck contracture caused by refractory urinary tract infection in elder.Methods 70 cases of bladder neck contracture were selected and randomly divided into two groups, 35 cases each.Two groups received Ceftriaxone sodium 1 g qd at acute episode,Levofloxacin Hydrochloride 0.5 g tid at non acute phase,control group received the treatment of urethral dilatation, Terazosin hydrochloride 10 mg qd, the experiment group received more with Tamsulosin Hydrochloride Sustained 0.2 mg qd.Two groups were both treated for four weeks.Urinary dynamics index, international prostate symptom score,quality of life score, clinical symptom disappearance time, the number of daily spasm and adverse reactions were compared.Results After treatment, the total effective rate in the experiment group(94.29%) was higher than the control group(65.71%)(P<0.05).Maximum and the average urinary flow rates in two groups increased after treatment(P<0.05), residual urine volume, maximum urethral closure pressure decreased(P<0.05), international prostate symptoms and quality of life score decreased(P<0.05); and compared with the control group, maximum and the average urinary flow rates in the experiment group were higher(P<0.05), residual urine volume, maximum urethral closure pressure were lower(P<0.05), international prostate symptoms and quality of life score were lower(P<0.05), and the average duration of symptoms of bladder neck spasm and the number of daily spasm in the experiment group were significantly shorter than the control group ( P <0.05 ).There was no significant difference in adverse reactions between the two groups. Conclusion Selectiveα1 adrenergic receptor blocking agent in the treatment of bladder neck contracture caused by refractory urinary tract infection in elder was effective, and it can improve the patient's urine flow rate, reduce the residual urine level, increase the quality of life.
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Objective To investigate the effects of β1-adrenergic receptor autoantibodies (β1-AA) on the proliferation of different subtypes of T lymphocytes in patients with heart failure .Methods β1-AA-positive IgG antibodies isolated from patients with heart failure were purified by using affinity chromatog -raphy.CD3 +CD4 +T and CD3 +CD8 +T lymphocytes were sorted by flow cytometry analysis .The prolifera-tion of different subtypes of T lymphocytes was tested by using CCK-8 kit.Tests for lactate dehydrogenase ( LDH) level and cell apoptosis were performed to evaluate T lymphocytes damage .Results The prolifera-tion of activated lymphocytes was inhibited by β1-AA isolated from the serum of patients with heart failure in a concentration dependent manner , but it could be blocked by β1 receptor blocker .The damage of lympho-cytes induced by β1-AA was increased.Moreover, β1-AA promoted the necrosis and apoptosis of CD 3 +CD4 +T and CD3 +CD8 +T lymphocytes and thus inhibited the proliferation of them .Conclusion β1-AA isolated from the serum of patients with heart failure inhibited the proliferation of CD 3 +CD4 +T and CD3 +CD8 +T lymphocytes through increasing the necrosis and apoptosis of them .This study suggests that β1-AA might induce immune disorders in addition to causing pathological changes in heart tissues .
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Objective To explore the relationship of autoantibodies against G protein coupled angiotensin Ⅱ-1 receptor (AT1 R),α1-adrenergic and β1-adrenergic receptors (α1 R and β1 R) with thyrotoxicosis heart disease (THD).Methods The epitopes of the second extracellular loop ofAT1 R (165-191),α1 R (192-218),and β1 R(197-222) were synthesized for screening autoantibodies from 277 participants by ELISA.237 patients with thyrotoxicosis were subdivided into thyrotoxicosis treatment group (n =148) and thyrotoxicosis recovery group (n =89),or into THD group (n =46) and simple hyperthyroidism group (n =191).40 healthy subjects were served as control group.Results (1) The positive rates of autoantibodies against AT1 R,α1 R and β1 R in thyrotoxicosis patients were higher than those in the control subjects (31.6％ vs 12.5％,27.8％ vs 10.0％,and 23.6％ vs 7.5％,all P＜0.05).The positive rates of the three autoantibodies in the patients with Graves' disease were higher compared with thyrotoxicosis caused by other reasons (36.3％ vs 19.7％,32.2％ vs 16.7％,and 28.1％ vs 12.1％,all P＜0.05).(2) In thyrotoxicosis treatment group,the positive rates of autoantibodies against AT1 R and α1 R were higher than those in the hyperthyroidism recovery group (40.5％ vs 16.9％ and 33.1％ vs 19.1％,both P＜0.05).(3) The incidence of autoantibodies against AT1 R and α1 R in THD were significantly higher compared with simple hyperthyroidism (52.2％ vs 26.7％ and 43.5％ vs 24.1％,both P＜0.05).Conclusions Autoantibodies against AT1 R,α1 R,and β1 R may play important roles in the pathogenesis of hyperthyroidism,which may be involved in the progression of THD.
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Objective To investigate the effects of autoantibodies (β1-AA) against second extra-cellular loop of the β1-adrenergic receptor (β1-AR-ECⅡ) in sera of patients with dilated cardiomyopathy (DCM) on proliferation of rat CD4+T lymphocytes.Methods β1-AA in the sera of patients with DCM was purified by affinity chromatography .CD4+T lymphocytes were isolated by immunomagnetic microbeads from peripheral blood mononuclear cells of rats and its positive rate was detected by flow cytometry .CCK-8 meth-od was used to detect the proliferation of CD 4+T lymphocytes and flow cytometry was performed to measure the ratio of CD4+/CD8+T lymphocyte .Results The purity of isolated rat CD 4+T lymphocytes by immu-nomagnetic microbeads reached 97.7%.The proliferation of CD4+T lymphocytes stimulated by CD3/CD28 was inhibited by β1-AA in a concentration-dependent manner .However , IgG antibodies extracted from sera of healthy controls did not suppress lymphocyte proliferation (P>0.05).The suppression effect of β1-AA was inhibited after binding to antigenic peptides corresponding to β1-AR-ECⅡ and was completely blocked by metoprolol, a specific antagonist of β1-adrenergic receptor (β1-AR).In addition,β1-AA had no effects on the ratio of CD4+/CD8+T lymphocyte .Conclusion β1-AA isolated from DCM patients suppresses the pro-liferation of CD4+T lymphocytes through β1-AR pathway , which indicates that β1-AA can directly reduce the number of T lymphocytes and impair the function of T lymphocytes , resulting in immune system disorders and the development of DCM .
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Although metoprolol is used to treat hypertension, clinical responses are variable and unpredictable. Evidence suggests that adrenergic 1 receptor (ADRB1, designated Adrb1 in rodents) gene polymorphisms influence the level of blood pressure response to this drug therapy, but their presence can not predict the response of the individual patient. The question exists whether epigenetic modifications, such as DNA methylation could cause changes in the gene’s expression that are a determining factor in metoprolol’s efficacy. The aim of this study was to verify whether DNA methylation could change the expression of the ADRB1 gene, and epigenetic modification could explain why individuals with identical ADRB1 gene polymorphisms have different antihypertensive responses to metoprolol. H9c2 rat myocardial cells in vitro were randomly divided into 5-aza-2'-deoxycytidine (decitabine)-treated (0.5 to 10.0 μM) and control groups. For the in vivo experiments, 45 spontaneously hypertensive rats (SHRs) were divided into metoprolol-treated and control groups, and after a 4-week intervention myocardia were harvested. Genomic methylation-sensitive PCR was used to assess the methylation status of the Adrb1 promoter after DNA extraction from H9c2 cells and SHR myocardia. Real-time fluorescent quantitative RT-PCR was used to determine levels of Adrb1 mRNA. In H9c2 cells, the least degree of methylation was observed in the 5.0 μM decitabine treated group. Prolonged exposure of cells to 5.0 μM decitabine resulted in downregulating methylation of the Adrb1 promoter. Increased levels of Adrb1 mRNA of the 5.0 μM group demonstrated that this concentration resulted in the highest expression. Accordingly, DNA methylation resulted in the downregulation of Adrb1 transcription. In vivo, the lower level of methylation of the Adrb1 promoter from SHR myocardial samples demonstrated a better antihypertensive effect by metoprolol. The expression of Adrb1 mRNA in the effective group of SHRs was significantly upregulated. In conclusion, as shown in both H9c2 cells and SHRs, downregulated methylation of the Adrb1 promoter is likely to improve the antihypertensive efficacy of metoprolol.
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Animals , Antihypertensive Agents/pharmacology , Cell Culture Techniques , DNA Methylation , Epigenesis, Genetic/genetics , Female , Humans , Metoprolol/pharmacology , Myocardium/metabolism , Random Allocation , Rats , Rats, Inbred SHR , Receptors, Adrenergic/genetics , Receptors, Adrenergic/metabolism , Receptors, Adrenergic, beta-1/genetics , Receptors, Adrenergic, beta-1/metabolismABSTRACT
BACKGROUND: The aim of this study was to evaluate the effect of diabetes on the function and distribution of vascular alpha1-adrenoceptors in the abdominal aorta and distal mesenteric artery from streptozotocin (STZ)-induced diabetic rats at the level of the alpha1-adrenoceptor subtypes. METHODS: Diabetes was induced by a single intravenous injection of STZ (60 mg/kg) in 8 week-old male Sprague-Dawley rats (n = 11). Age-matched normal rats (n = 14) were used as a control group. Four weeks after STZ injection, the tilting-induced change of the mean arterial pressure was recorded. The alpha1-adrenoceptor subtypes mediating the contractions of the distal mesenteric artery and abdominal aorta were investigated using the agonist phenylephrine and subtype-selective antagonists that included prazocin, 5-methylurapidil and BMY 7378. The expressions of the alpha1-adrenoceptor subtypes of each artery were examined by immunofluorescence staining using the subtype selective antibodies. RESULTS: The recovery of the mean arterial pressure was delayed after positional change in the diabetic rats. Compared with that of the normal rats, the contractile response to phenylephrine was increased in the abdominal aortas and it was decreased in the distal mesenteric arteries in the diabetic rats. In addition, compared with the normal rats, the fluorescent intensity of all the alpha1-adrenoceptor subtypes was increased in the abdominal aortas and it was decreased in the mesenteric arteries of the diabetic rats. CONCLUSIONS: Diabetes increased the contractility of the abdominal aorta in response to phenylephrine, yet diabetes decreased that of the mesenteric arteries in the STZ-induced diabetic rats. Those results are mainly based on the overall change of the alpha1-adrenoceptor, and not on the change of the specific alpha1-adrenoceptor subtypes.
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Animals , Humans , Male , Rats , Aorta, Abdominal , Arterial Pressure , Arteries , Contracts , Diabetes Complications , Diabetes Mellitus, Experimental , Fluorescent Antibody Technique , Injections, Intravenous , Mesenteric Arteries , Negotiating , Phenylephrine , Piperazines , Rats, Sprague-Dawley , Receptors, Adrenergic, alpha-1 , StreptozocinABSTRACT
BACKGROUND: The hemodynamic responses to endotracheal intubation are associated with sympathoadrenal activity. Polymorphisms in the beta1-adrenergic receptor (beta1AR) gene can alter the pathophysiology of specific diseases. The aim of this study is to investigate whether the Ser49Gly and Arg389Gly polymorphism of the beta1AR gene have different cardiovascular responses during endotracheal intubation under sevoflurane anesthesia. METHODS: Ninety-one healthy patients undergoing general anesthesia were enrolled. Patients underwent slow inhalation induction of anesthesia using sevoflurane in 100% oxygen. Vecuronium 0.15 mg/kg was given for muscle relaxation. Endotracheal intubation was performed by an anesthesiologist. The mean arterial pressure (MAP), heart rate (HR), and the corrected QT (QTc) interval were measured before induction, before laryngoscopy, and immediately after tracheal intubation. Genomic DNA was isolated from the patients' peripheral blood and then evaluated for the beta1AR-49 and beta1AR-389 genes using an allele-specific polymerase chain reaction method. RESULTS: No differences were found in the baseline values of MAP, HR, and the QTc interval among beta1AR-49 and beta1AR-389, respectively. In the case of beta1AR-49, the QTc interval change immediately after tracheal intubation was significantly greater in Ser/Ser genotypes than in Ser/Gly genotypes. No differences were observed immediately after tracheal intubation in MAP and HR for beta1AR-49 and beta1AR-389. CONCLUSIONS: We found an association between the Ser49 homozygote gene of beta1AR-49 polymorphism and increased QTc prolongation during endotracheal intubation with sevoflurane anesthesia. Thus, beta1AR-49 polymorphism may be useful in predicting the risk of arrhythmia during endotracheal intubation in patients with long QT syndrome.
Subject(s)
Humans , Anesthesia , Anesthesia, General , Arrhythmias, Cardiac , Arterial Pressure , DNA , Genotype , Heart Rate , Hemodynamics , Homozygote , Inhalation , Intubation , Intubation, Intratracheal , Laryngoscopy , Long QT Syndrome , Methyl Ethers , Muscle Relaxation , Oxygen , Polymerase Chain Reaction , Vecuronium BromideABSTRACT
BACKGROUND: The purpose of this study was to evaluate the gender-related changes in the function and distribution of alpha1-adrenoceptors in the distal mesenteric artery of streptozotocin (STZ)-induced diabetic rats at the level of alpha1-adrenoceptor subtypes. METHODS: Diabetes was induced by intravenous injection of STZ in a dose of 60 mg/kg through the tail vein in 8 week-old male or female Sprague-Dawley rats (n = 13/group). Age-matched normal rats (n = 15) were used as a control group. Four weeks after STZ injection, the change in mean arterial pressure caused by a 45degrees tilting was recorded. The alpha1-adrenoceptor subtypes mediating contractions of the distal mesenteric artery were investigated using the agonist, phenylephrine as well as subtype-selective antagonists including prazocin, 5-methylurapidil, and BMY 7378. The expression of alpha1-adrenoceptor subtypes of each artery was examined by immunofluorescence staining and western blotting using subtype selective antibodies. RESULTS: Compared with normal male rats, the contractile response to phenylephrine was decreased in the distal mesenteric artery in normal female rats. Moreover, a decrease in contractile force was observed in STZ-induced diabetic rats compared with age-matched controls. Western blotting revealed that there was the difference between normal male and female rats in manifestation of the alpha1D-adrenoceptor. In STZ-induced male and female diabetic rats, all alpha1-adrenoceptor subtypes were decreased in distal mesenteric arteries, compared with normal rats. CONCLUSIONS: There was the gender-related functional difference of alpha1-adrenoceptors in normal rats. In both male and female rats, diabetes decreased the contractile response in mesenteric arteries, which might be caused by the overall change in alpha1-adrenoceptor.
Subject(s)
Animals , Female , Humans , Male , Rats , Arterial Pressure , Arteries , Blotting, Western , Contracts , Diabetes Mellitus, Experimental , Fluorescent Antibody Technique , Injections, Intravenous , Mesenteric Arteries , Negotiating , Phenylephrine , Piperazines , Rats, Sprague-Dawley , Receptors, Adrenergic, alpha-1 , Streptozocin , VeinsABSTRACT
Background & objectives: Several studies reported the polymorphisms of β1-adrenergic receptor gene in healthy volunteers and its influence on cardiovascular disorders. We investigated the genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism in healthy volunteers of South Indian Tamilian population vis-à-vis other major ethnic groups. Methods: The genetic variants were determined by using Taqman 5’ nuclease assay- real time PCR analysis in 533 normal healthy volunteers (18-60 yr; M=290; F=243). The allelic discrimination analysis was done by 7700 SDS software. Results: The estimated genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism were compared with other major populations. The frequencies of the variant alleles Gly49 and Gly389 were 15.1 and 25.8 per cent respectively. Interpretation & conclusions: Our study shows that interethnic variation exists in the polymorphisms of β1-adrenergic receptor gene and the results generated in this study might serve as a genetic marker for further studies in Tamilian (South India) population.
Subject(s)
Adult , Amino Acid Substitution/genetics , Ethnicity/genetics , Female , Gene Frequency , Genotype , Humans , India , Male , Middle Aged , Polymerase Chain Reaction/methods , Polymorphism, Genetic , Receptors, Adrenergic, beta-1/genetics , Young AdultABSTRACT
Ohjective To investigate the associations between the Arg389Gly polymorphism of the β_1-adrenergiecreceptor gene (ADRB1) and vasovagal syncope (VVS) in Chinese children. Methods Genotype of ADRB1 was determined by polymerase chain reaction-restriction fragment length pelymorphism analysis. Case-control studies and quantitative trait analysis were carried out by comparing between carriers (one or two copies of the Gly389 allele) and non-carriers (Arg389 genotype) of the ADRBI in 54 patients with unexplained syncope and in 54 healthy control subjects. Patients were subdivided into two groups according to head up tilt test (HUTT) : positive HUTT, known as VVS group and negative HUTT group. Distribution of Arg389Gly genetype in VVS group and the relationship to three clinical patterns were also analyzed. Results An allele frequency of Arg389 was 73.15% and Gly389 was 26.85% in healthy subjects. Higher Gly389 allele frequency was found in VVS group (n = 30) than that in negative HUTT group (33.33% vs. 14.58%, P < 0.05). In VVS group, the frequencies of the Gly389 allele in cardioinhibitory pattern (n = 6), mixed pattern (n = 9) and vasodepressor pattern (n = 15) was 66.67%, 33.3% and 23.33%, respectively, which had significant differences between the cardioinhibitory pattern from any of the other two patterns (both P < 0.05). Conclusions An association of positive HUTT with a single nucleotide pelymorphism of Gly to Arg switch at position 389 of the ADRB1 was found. This polymorphism may contribute to susceptibility to VVS.