Effects of Isoprenaline，Phenylephrine on Heart and Influence of Nifedipine on These Effects

In a perfused isovolumetrically contracting rat heart model, the effects of isoprenaline(IPN) and phenylephrine (PE) on myocardial contraction and relaxation were investigated,and the influence of nifedipine on these effects was studied. Both IPN and PE increased the myocardial contraction and improved its relaxation, but some differences existed.Nifedipine (10 nmol/L)substantially inhibited the PE-mediated inotropic effect, but in case of IPN-mediated inotropic ones, it did not.It was assumed that there may be various types of slow channels, one was activated by IPN,and the other, by PE.

STEREOSELECTIVE EFFECT OF PROPRANOLOL ON ANTIPYRINE METABOLISM AND ISOPRENALINEINDUCED TACHYCARDIA IN RABBITS

The effects of l-, d- and dl-propranolol on antipyrine metabolism and isoprenaline-induced tachycardia were studied in rabbits. The plasma concentration of antipyrine was assayed by Brodie’s spectrophotometric method and the change of heart rate was evaluated by ECG. Both isomers of propranolol hydrochloride were administered iv （800 μg/kg） to the rabbits. d-propranolol produced an antipyrine t 1/2 of 2.67±0.77h and a cl of 0.49±0.1 l/h while its levo-form produced an antipyrine t 1/2 of 1.7±0.39h and a cl of 0.88±0.22 l/h. The differences between the half-lives and between the clearances were statistically significant （P【0.05 for t 1/2, P【0.01 for cl）. The inhibitory effects of l- and d-propranolol on isoprenaline-induced tachycardia were assessed. l-propranolol yielded an ID50 which was only 1/88 of d-propranolol’s. Our studies showed that the β-receptor blocking activity of propranolol mainly came. from its levoform while the effect on antipyrine metabolism came from its dextro-form.

Pleiotropic attenuating effect of Ginkgo biloba against isoprenalineinduced myocardial infarction via improving Bcl-2/mTOR/ERK1/2/Na+ , K+ -ATPase activities

Objective:Myocardial infarction(MI)is linked to an imbalance in the supply and demand of blood oxygen in the heart muscles.Beta-blockers and calcium antagonists are just two of the common medications used to treat MI.However,these have reportedly been shown to be either ineffective or to have undesirable side effects.Extract of Ginkgo biloba leaves(GBE),a Chinese herbal product offers special compatibility benefits in therapeutic settings relating to inflammatory diseases and oxidative stress.In order to better understand how GBE affects MI in rats insulted by isoprenaline(ISO),the current study was designed.Methods:The heart weight index,serum lipid profile,cardiac marker enzymes,endogenous antioxidants[catalase(CAT),superoxide dismutase(SOD),glutathione(GSH),nitrites and malondialdehyde(MDA)],inflammatory mediators[tumour necrosis factor alpha(TNF-a)and interleukin-6(IL-6)],immunohistochemical expressions of B-cell lymphoma factor-2(Bcl-2),extracellular signal-regulated kinase(ERK1/2),and mammalian target of rapamycin(mTOR)and histopathological analysis were used to assess the cardioprotective properties of GBE.Results:The findings showed that GBE effectively attenuated myocardial infarction by boosting the body’s natural antioxidant defense system and reducing the release of inflammatory cytokines as well as heart injury marker enzymes.The expression of Bcl-2,ERK1/2 and mTOR was increased while the histomorphological alterations were reversed.Conclusion:The cardioprotective effects of GBE may be due to a mechanism involving increased Bcl-2/mTOR/ERK1/2/Na^(+),K^(+)-ATPase activity.

MicroRNA-34c-5p provokes isoprenaline-induced cardiac hypertrophy by modulating autophagy via targeting ATG4B

Pathological cardiac hypertrophy serves as a significant foundation for cardiac dysfunction and heart failure. Recently, growing evidence has revealed that microRNAs(miRNAs) play multiple roles in biological processes and participate in cardiovascular diseases. In the present research, we investigate the impact of miRNA-34 c-5 p on cardiac hypertrophy and the mechanism involved. The expression of miR-34 c-5 p was proved to be elevated in heart tissues from isoprenaline(ISO)-infused mice. ISO also promoted miR-34 c-5 p level in primary cultures of neonatal rat cardiomyocytes(NRCMs). Transfection with miR-34 c-5 p mimic enhanced cell surface area and expression levels of foetal-type genes atrial natriuretic factor(Anf) and β-myosin heavy chain(β-Mhc) in NRCMs. In contrast, treatment with miR-34 c-5 p inhibitor attenuated ISO-induced hypertrophic responses. Enforced expression of miR-34 c-5 p by tail intravenous injection of its agomir led to cardiac dysfunction and hypertrophy in mice, whereas inhibiting miR-34 c-5 p by specific antagomir could protect the animals against ISO-triggered hypertrophic abnormalities. Mechanistically, miR-34 c-5 p suppressed autophagic flux in cardiomyocytes, which contributed to the development of hypertrophy. Furthermore, the autophagy-related gene 4 B(ATG4 B) was identified as a direct target of miR-34 c-5 p, and miR-34 c-5 p was certified to interact with 3’untranslated region of Atg4 b mRNA by dual-luciferase reporter assay. miR-34 c-5 p reduced the expression of ATG4 B, thereby resulting in decreased autophagy activity and induction of hypertrophy. Inhibition of miR-34 c-5 p abolished the detrimental effects of ISO by restoring ATG4 B and increasing autophagy. In conclusion, our findings illuminate that miR-34 c-5 p participates in ISO-induced cardiac hypertrophy, at least partly through suppressing ATG4 B and autophagy. It suggests that regulation of miR-34 c-5 p may offer a new way for handling hypertrophy-related cardiac dysfunction.

MicroRNA-210 Plays a Critical Role in the Angiogenic Effect of Isoprenaline on Human Umbilical Vein Endothelial Cells via Regulation of Noncoding RNAs

Background：β-adrenoceptors play a crucial regulatory role in blood vessel endothelial cells.Isoprenaline （ISO,a β-adrenergic agonist） has been reported to promote angiogenesis through upregulation of vascular endothelial growth factor （VEGF） expression;however,the underlying mechanism remains to be investigated.It is widely accepted that certain noncoding RNAs,including microRNAs （miRNAs） and long noncoding RNAs （lncRNAs）,can regulate endothelial cell behavior,including their involvement in angiogenesis.Therefore,we aimed to investigate whether noncoding RNAs participate in ISO-mediated angiogenesis using human umbilical vein endothelial cells （HUVECs）.Methods：We evaluated VEGF-A messenger RNA （mRNA） and protein levels in ISO-treated HUVECs by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay,respectively.To establish whether noncoding RNAs are associated with ISO-mediated angiogenesis,we measured expression of the miRNAs miR-210,miR-21,and miR-l,as well as that of the lncRNAs growth arrest-specific transcript 5 （GAS5）,maternally expressed 3 （MEG3）,and metastasis-associated lung adenocarcinoma transcript 1 （MALAT1） in HUVECs exposed to ISO.Furthermore,to ascertain its importance in ISO-mediated angiogenesis,we constructed the HUVECs with overexpressing miR-210 and detected the subsequent expression of VEGF-A and noncoding RNAs.All statistical analyses were performed using SPSS 16.0 software.Intergroup comparisons were carried out by one-way analysis of variance.Results：VEGF-A mRNA levels were elevated in the ISO group （1.57 ± 0.09） compared to those in the control group （P 〈 0.01）.Moreover,concentrations of VEGF-A in culture supernatants significantly differed between the control （113.00 ± 19.21 pg/ml） and ISO groups （287.00 ± 20.27 pg/ml;P 〈 0.01）.Expression of miR-1,miR-21,and miR-210 was higher （3.89 ± 0.44,2.87 ± 087,and 3.33 ± 1.31,respectively） in ISO-treated cells than that in controls （P 〈 0.01）,whereas that of GAS5 and MEG3 （0.22 ± 0.10 and 0.58 ± 0.16,respectively） was lower as a result of ISO administration （P 〈 0.05）.There was no significant difference in the expression of MALAT1 between the groups.Interestingly,miR-210 overexpression heightened the levels of VEGF-A and miR-21 （5.87 ± 1.24 and 2.74 ± 1.15,respectively;P 〈 0.01） and reduced those of GAS5 and MEG3 （0.19 ± 0.01 and 0.09 ± 0.05,respectively;P 〈 0.01）.Conclusions：ISO-mediated angiogenesis was associated with altered expression of miR-210,miR-21,and the lncRNAs GAS5 and MEG3.The effects ofmiR-210 on the expression of VEGF-A and noncoding RNAs were similar to those of ISO,indicating that it might play an important role in ISO-mediated angiogenesis.

Separation of chiral drugs with β-CD phosphate by capillary electrophoresis

β-Cyclodextrin phosphate (β-CD-phosphate) was used as a selector for separating chiral drugs by capillary electrophoresis (CE). A solution comprising of 120 mmol/L Britton Robinson buffer (BRB) containing 10 mmol/L 0-CD phosphate with the pH adjusted to 7.0 was used as the background electrolyte (BGE), and a small amount of analyte was injected (600v/1s). Triethylamine, diethylamine, triethanolamine, diethanolamine, Tris added as modifier were compared. Isoprenaline, methoxamine, oxprenolol, practolol were successfully resolved.

EFFECT OF THE EXCITATION OF ADRENOCEPTORS ON THE PACEMAKER CURRENT I_f OF SHEEP CARDIAC PURKINJE FIBRES IN “ISCHEMIA” SOLUTIO

ＥＦＦＥＣＴＯＦＴＨＥＥＸＣＩＴＡＴＩＯＮＯＦＡＤＲＥＮＯＣＥＰＴＯＲＳＯＮＴＨＥＰＡＣＥＭＡＫＥＲＣＵＲＲＥＮＴＩ_ｆＯＦＳＨＥＥＰＣＡＲＤＩＡＣＰＵＲＫＩＮＪＥＦＩＢＲＥＳＩＮ“ＩＳＣＨＥＭＩＡ”ＳＯＬＵＴＩＯＮＸｕＹｏｕｑｉｕ（徐有秋），Ｚｈａ?..

Tako-tsubo cardiomyopathy in a male patient after administration of isoproterenol and implantation of a pacemaker

Background: Tako-tsubo cardiomyopathy occurs typicallly after an intrinsic adrenergic hyperstimulation triggered by a psychological or physically stressful event. Exceptionally, it may be caused by an exogenous hyperadrenergism. We report the case of an 85 year old man, hypertensive, with a history of ischemic stroke. He consulted for signs of heart failure with recurrent dizziness two weeks which was explained by an atrioventricular block. Initial echocardiography showed left ventricular ejection fraction to 60% with no wall motion abnormalities. The patient received iso-prenaline (0.02 mcg/kg/mn) for 20 hours before the implantation of a single chamber pacemaker. At 24 hours of admission an acute pulmonary edema occurred. The control echocardiography showed impaired left ventricular ejection fraction of 25% with apical ballooning and akinesis was also found on ventricu-lography. Coronary angiography showed no significant coronary lesions. Troponin level was elevated to 2 ng/ml. The pulmonary edema was then controlled. Subsequent clinical and echocardiographic were favo- rable after two weeks which was consistent with the diagnosis of tako-tsubo cardiomyopathy. Conclusion: This case illustrates an example of tako-tsubo syndrome induced by an exogenous catecholergic stimulation (isoprenaline) combined with an endogenous release after a pacemaker implantation which confirmed the physiopathological hypothesis of a catecholamine-mediated stunning in tako-tsubo cardiomyopathy.

Protective effect of different medicinal parts of Lonicera japonica Thunb. on myocardial ischemic injury induced by isoproterenol in rats

Background:To study the protective effect of different medicinal parts of honeysuckle on myocardial ischemia injury in rats.Method:SD mice were randomly divided into 6 groups:the normal group,model group,compound salvia miltiorrhiza group,Lonicera japonica Thunb.of flower bud group,flower group,and the stem leaf group.There were 8 rats in each group,including 4 males and 4 females.The normal group and model group were given equal amount of distilled water,whereas the other dosage groups were given the appropriate drug by intragastric administration,continuous gavage for 14 days.From the 12 days,in addition to the normal group were injected of the same amount of normal saline,the other groups were injected with 5g/kg.Injection of isoproterenol to establish the mouce mycardial ischemia model,its continuously 3d.To detect the serum of AST,CK,CK-MB,LDH and the myocardial issue of Chinese super oxideismutase and malondialdehyde level.Results:Compared with normal group,the levels of AST,CK,CK-MB,cTn-I,LDH and malondialdehyde were significantly increased in the model group(P<0.01)and the level of super oxideismutase decreased significantly(P<0.01)the levels of AST,CK,CK-MB,cTn-I,LDH and malondialdehyde in the serum of flower bud group,flower group and stem leaf group were significantly decreased(P<0.05),and the decreasing level of flower bud group,flower,leaf group of AST,CK,CK-MB,cTn-I,LDH and malondialdehyde was flower bud group>flower>leaf group,the activity of super oxideismutase was obviously increased,and the activity level of super oxideismutase of flower bud group,flower group and stem leaf group was flower bud group>flower>leaf group.Conclusion:In the myocardial ischemic injury model of rats induced by isoproterenol,Lonicera japonica Thunb.had a protective effect in all parts,and Lonicera japonica Thunb.bud had the greatest protective effect.