AIMTo study the regular pattern and mechanism of positive inotropic effect after washout of ACh (rebound of myocardial contractile force) in isolated rabbit hearts.

METHODSThe changes of myocardial contractile force after perfusion and washout of ACh were observed in isolated Langendorff perfused rabbit hearts.

RESULTSMaximum rebound rate induced by ACh of 10(-8)-10(-3) mol/L were 2.20% +/- 1.70%, 6.71% +/- 3.40%, 9.18% +/- 3.54%, 14.16% +/- 3.27%, 4.37% +/- 5.86% and 1.03% +/- 6.86%, respectively. Compared with the ACh of 10(-5) mol/L in control group, adrenaline enhanced rebound of myocardial contractile force, maximum rebound rate in adrenaline group was 29.25% +/- 5.83% (P < 0.05), propranolol reduced rebound, and maximum rebound rate in propranolol group was 5.15% +/- 4.45% (P < 0.05), we had not detected rebound of myocardial contractile force in 800 s after addition ACh in verapamil group.

CONCLUSIONIn isolated rabbit heart, positive inotropic effect after washout of ACh has relevance to the activities of calcium current channel and beta-adrenergic receptor. Perhaps there are some different aspects in the mechanism of positive inotropic effect between perfusion of high concentration and after washout of ACh.

Acetylcholine ; pharmacology ; Animals ; Cardiotonic Agents ; pharmacology ; Heart ; drug effects ; In Vitro Techniques ; Myocardial Contraction ; drug effects ; physiology ; Rabbits

Action Potentials ; drug effects ; physiology ; Animals ; Guinea Pigs ; Heart Ventricles ; drug effects ; Lysophospholipids ; pharmacology ; Myocardial Contraction ; drug effects ; physiology ; Myocardium ; Sphingosine ; analogs & derivatives ; pharmacology

Action Potentials ; drug effects ; Animals ; Estradiol ; pharmacology ; Female ; Guinea Pigs ; Heart Ventricles ; cytology ; Myocardial Contraction ; drug effects ; Papillary Muscles ; drug effects ; physiology ; Progesterone ; pharmacology

AIMTo explore whether endogenous catecholamine participates in the effect of interleukin-2 on the isolated heart.

METHODSThe number of premature ventricular contraction (PVC), left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure(LVEDP), heart rate (HR) and coronary flow(CF)were recorded in isolated Langendorff perfused rat hearts.

RESULTS(1) 50 U/ml IL-2 increased the PVC number, LVDP LVEDP, HR and CF. (2) Pretreatment of reserpine or propranolol abolished the cardiac effect of IL-2 at 50 U/ml, while pretreatment with phentolamine did not change the effect of IL-2. (3) 200 U/ml IL-2 increased the number of PVC,but did not increase LVDP, LVEDP, HR and CF. (4) After pretreatment of reserpine or propranolol, IL-2 failed to increase the number of PVC, but caused decrease of LVDP, HR and CF, and elevation of LVEDP.

CONCLUSIONEndogenous catecholamine mediates the arrhythmogenic, positively chronotropic and inotropic effects of IL-2. IL-2 at 200 U/ml inhibits the cardiac function in the isolated rat heart.

Animals ; Catecholamines ; physiology ; Heart ; drug effects ; physiology ; In Vitro Techniques ; Interleukin-2 ; pharmacology ; Male ; Myocardial Contraction ; drug effects ; Rats ; Rats, Sprague-Dawley

AIMTo investigate the effects of endothelin-1 (ET-1) and nitric oxide (NO) on lipopolysaccharide(LPS)-induced myocardial dysfunction, and explore the related underlying mechanisms.

METHODSExperimental septic model was established by intraperitoneal injection of LPS (10 mg x kg(-1)). The study was carried out on the isolated rat hearts to determine the roles of ET-1 and NO in the effect of LPS on the cardiac contractility and on the isolated rat ventricular myocytes model to observe the [Ca2+]i homeostasis in cardiac myocytes.

RESULTS(1) The levels of serum NO2-/NO3- and plasma ET-1 were markedly increased by LPS treatment for 4 hours. (2) LPS induced the decrease in rate-pressure product (RPP), and increase in left ventricular end-diastolic pressure (LVEDP) in the isolated perfused rat hearts. Pretreatment with either aminoguanidine (AMG) (100 mg x kg(-1), i.p.) or BQ-123 (1 mg x kg(-1), i.p.) partially attenuated LPS-induced myocardial depression. When these two drugs were simultaneously given, myocardial depression elicited by LPS was almost abolished. (3) LPS significantly decreased the amplitude of caffeine induced [Ca2+]i transients compared to the control cells. The activity of SR Ca22+ -ATPase was significantly decreased in the cardiac myocytes from LPS-treated rats. Single pretreatment with either AMG or BQ-123 did not attenuate the impairment of SR Ca2+ -ATPase induced by LPS.

CONCLUSIONET-1 and NO mediate myocardial dysfunction in hearts isolated and decrease [Ca2+]i transients in cardiac myocytes from LPS-treated rats. But neither ET-1 nor NO participates in the impairment of SR Ca2+ -ATPase induced by LPS.

Animals ; Depression, Chemical ; Endothelin-1 ; physiology ; Lipopolysaccharides ; toxicity ; Male ; Myocardial Contraction ; drug effects ; physiology ; Nitric Oxide ; physiology ; Rats ; Rats, Sprague-Dawley ; Shock, Septic ; chemically induced ; physiopathology

OBJECTIVETo investigate the cardiac effect of interleukin-2 (IL-2) and to explore the underlying mechanism.

METHODSThe video tracking system and spectrofluorometric method were used to measure the cell contraction and intracellular calcium. Fura-2/AM was used as a calcium fluorescence probe. Langendorff perfusion technique was used to determine the effect of IL-2 on the intact heart.

RESULTSCompared with the control group, IL-2 5 U/ml, 50 U/ml significantly decreased cell contraction amplitude [(74.95+/-4.79) vs (98.09+/-5.02)%, (64.30+/-5.24) vs (97.38+/-4.05)%], peak velocity of cell shortening [(70.23+/-4.85)% vs (98.09+/-5.46)%, (61.15+/-5.20)% vs (97.38+/-6.85)%], peak velocity of cell relengthening [(71.22+/-4.79)% vs (98.32+/-6.08)%, (68.16+/-5.24)% vs (97.55+/-5.00)%] and end- diastolic cell length [(88.28+/-5.84)% vs (97.95+/-5.52)%, (84.18+/-6.52)% vs (98.94+/-6.76)%]. IL-2 (5 U/ml, 50 U/ml) also markedly inhibited intracellular calcium transient [(74.94+/-4.90)% vs (98.09+/-3.74)%,(71.00+/-5.28)% vs (97.38+/-5.52)%], and elevated end-diastolic calcium level of ventricular myocytes [(113.91+/-5.93)% vs (100.10+/-3.02)%, (119.09+/-7.12)% vs (100.52+/-6.00)%], which were attenuated by the opioid receptor antagonist naloxone (Nal,10 nmol/L). In the isolated perfused rat heart,when compared with the control group, IL-2 50 U/ml markedly decreased left ventricular developed pressure [(79.91+/-2.18) vs (93.84+/-2.94)mmHg], maximal rate of rise of left ventricular pressure [(2370.7358.29) vs (2591.50+/-62.81)mmHg] maximal rate of fall of left ventricular [-(1460.95+/-38.6) vs -(1634.24+/-54.05) mmHg/s] and heart rate [(217.35+/-10.56) vs (244.52+/-11.23) beats/min], but increased left ventricular end-diastolic pressure (11.44+/-1.02 vs 9.23+/-0.46). Pretreatment with Nal (10 nmol/L) antagonized the cardiac depression and left ventricular end-diastolic pressure elevation induced by IL-2.

CONCLUSIONThe cardiac effect of IL-2 is mediated by opioid receptors on the membrane of cardiomyocytes.

Animals ; Calcium ; metabolism ; Depression, Chemical ; In Vitro Techniques ; Interleukin-2 ; pharmacology ; Male ; Myocardial Contraction ; drug effects ; Naloxone ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, kappa ; drug effects ; physiology

AIMTo investigate the effects of interleukin-2 (IL-2) on the transmembrane potential and contractile force in ventricular papillary muscle of rat and the underlying mechanism.

METHODSThe transmembrane potentials and contractile force were recorded by intracellular glass microelectrode and tension transducer in the isolated rat papillary muscles.

RESULTS(1) IL-2 shortened the action potential duration (APD50 and APD80), while had no effects on resting potential, action potential amplitude and depolarization rate. (2) IL-2 depressed the contractile force of the muscle in dose-dependent manner. IL-2 at concentrations of 0.5, 2.5, 10, 50 and 200 u/ml decreased the developed tension to 94.8% (P < 0.05), 85.8%, 76.3%, 69.3% and 52.5% (P < 0.01), respectively. (3) Pretreatment with L-NAME (10(-4) mol/L) attenuated the negative inotropic effect of IL-2, in which effect of IL-2 at concentrations from 0.5 to 10 u/ml was completely abolished, and the effect of IL-2 at high dose (50 and 200 u/ml) was partly attenuated by L-NAME.

CONCLUSIONIL-2 had inhibitory effects on action potential duration and contractile force of papillary muscle, and its negative inotropic effect was mediated by nitric oxide.

Action Potentials ; drug effects ; Animals ; Heart Ventricles ; drug effects ; Interleukin-2 ; pharmacology ; Male ; Myocardial Contraction ; drug effects ; physiology ; Nitric Oxide ; metabolism ; Papillary Muscles ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the protective effects of tetramethylpyrazine (TMPZ) on rat myocardial cells infected by Coxsackie virus B3 (CVB3) and its signal transduction mechanism.

METHODSThe cultured myocardial cells of neonatal Sprague-Dawley rats were randomly treated with CVB3, CVB3+TMPZ (100 micromol/L), TMPZ (100 micromol/L) (negative control) or DMEM (blank control). After treatment, the beating rate of myocardial cells and the LDH activity in the culture fluid were measured. Cell viability was ascertained with MTT assay. Western blot was used to study the expression of nuclear factor kappa-B (NF-kappaB) protein in myocardial cells.

RESULTSThe beating rate of myocardial cells in the untreated CVB3 infection group was significantly lower than that in the TMPZ-treated CVB3 infection group (32.0+/-3.6 bpm vs 84.3+/-3.5 bpm, P<0.01). The LDH activity and NF-kappaB expression in the TMPZ-treated CVB3 infection group was significantly reduced when compared with untreated CVB3 infection group (P<0.05, P<0.01, respectively). Cell viability 7 days after CVB3 infection in the TMPZ-treated group was higher than that in the untreated CVB3 infection group (86.7+/-2.7% vs 35.3+/-3.4%; P<0.01).

CONCLUSIONSTMPZ can provide protective effects on rat myocardial cells infected by CVB3, possibly by an inhibition of the activity of NF-kappaB in myocardial cells.

Animals ; Cytoprotection ; Enterovirus B, Human ; L-Lactate Dehydrogenase ; metabolism ; Myocardial Contraction ; drug effects ; Myocarditis ; drug therapy ; Myocytes, Cardiac ; drug effects ; virology ; NF-kappa B ; analysis ; physiology ; Pyrazines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; physiology

OBJECTIVETo study the vasodilation effects of the Total alkali Sophora alopecuroids L (TASa) on rabbit thoracic aortic rings in vitro and the possible mechanisms.

METHODRabbit aortic rings were isolated and precontracted with noradrenaline (NA) and then were divided into six groups including control group, TASa group, TASa + 1 x 10(-5) mol x L(-1) indomethacin (Indo), TASa + 1 x 10(-5) mol x L(-1) propranolol (Prop), TASa + 1 x 10(-10 mol x L(-1) N(omega)-nitro-L-arginine (L-NNA), TASa + removal of endothelium. The vasodilation effects of TASa were investigated. In addition, the thoracic aortic rings were pre-treated with TASa (40 mg x L(-1)) and then the thoracic aortic rings were treated with cumulative NA (110(-8)-110(-5) mol x L(-1)), KCl (6.3-100 mmol x L(-1)) or CaCl2 (110(-5)-110(-2) mol x L(-1)). The dose response curves of aortic rings were recorded.

RESULTTASa can relax isolated rabbit aorta and has an obvious concentration-dependent relaxation (r = 0.94, P < 0.01). The relaxant effect of TASa was no significant reducing by removal of endothelium and by treatment with L-NNA, Indo or Prop. In addition, TASa can decrease the dose response curves of aortic rings to NA, KCl or CaCl2.

CONCLUSIONThe vasodilation effects of TASa are related to not only inhibition of intracellular calcium release, but also reduction to calcium flow to the interior of the cell with blockage of calcium channels.

Alkalies ; pharmacology ; Animals ; Aorta, Thoracic ; drug effects ; physiology ; Female ; In Vitro Techniques ; Male ; Muscle, Smooth, Vascular ; drug effects ; physiology ; Myocardial Contraction ; drug effects ; Plant Extracts ; chemistry ; pharmacology ; Rabbits ; Sophora ; chemistry ; Vasodilator Agents ; chemistry ; pharmacology

The present study is aimed to study the effect of sarcoplasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) gene transfer on the contractile function of isolated cardiomyocytes of canines. The cardiomyocytes were isolated with collagenases. The isolated cardiac cells were divided into untransfected group, empty vector group and SERCA2a-transfected group. Recombinant adenovirus vector carrying enhanced green fluorescent protein gene was used for SERCA2a gene delivery. The expression of SERCA2a protein in cardiomyocytes was determined by Western blot. Contractile function of cardiomyocytes was measured with motion edge-detection system of single cell at 48 h after transfection. The results showed, compared with untransfected group, SERCA2a protein level, percentage of peak contraction amplitude under normal condition, percentages of peak contraction amplitude under Ca(2+) or isoproterenol stimulation, time-to-peak contraction (TTP) and time-to-50% relaxation (R50) in SERCA2a-transfected group all increased significantly. While all the above indices in empty vector group did not show any differences with those in untransfected group. These results suggest that the overexpression of SERCA2a by gene transfer may enhance the contraction function of canine myocardial cells.
Adenoviridae ; genetics ; metabolism ; Animals ; Dogs ; Male ; Myocardial Contraction ; drug effects ; physiology ; Myocytes, Cardiac ; metabolism ; Recombinant Proteins ; genetics ; metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; genetics ; metabolism ; Transfection