Effect of BQ123 on the voltage-gated K+ current of pulmonary artery smooth muscle cells of rats exposed to chronic hypoxia

AIM:To study the effect of BQ123 on voltage-gated K+ current in pulmonary artery smooth muscle cells (PASMCs) from chronic hypoxic rats. METHODS:Twelve age and body weight matched Wistar rats were randomly divided into control and chronic hypoxic group. Single PASMCs were obtained with acute enzyme (collagnaseⅠ plus papain) dispersing method. Using the whole cell patch-clamp technique in freshly isolated PASMCs from normorxic and hypoxic rats, the effects of ET-1 and BQ123, a selective ETA receptor antagonist, on voltage-gated K+ current were recorded. RESULTS:(1) ET-1 (10-8 mol·L-1) caused inhibition of K+ current in PASMCs from normoxic and hypoxic rats. The effect of ET-1 on K+ current in PASMCs from hypoxic rats was greater than that from normoxic rats ［+50 mV, percent inhibition were (71.04±6.58)% and (60.21±5.32)%, respectively, P<0.01, n=6］. (2) In normoxic PASMCs, neither BQ123 alone produced influence on the IKV (P>0.05, n=5), nor ETA receptor blockade had change of ET-1 mediated IKV inhibition. (3) In chronic hypoxic PASMCs, BQ123 significantly reduced the effect of ET-1 mediated IKV inhibition, from (28.49±6.69) pA/pF to (74.19±9.74) pA/pF at +50 mV (P<0.01, n=6). CONCLUSION:In normoxic condition, the effect of ET-1 on IKV of PASMCs is not mediated by BQ123, a selective ETA receptor antagonist. During exposure to chronic hypoxia, the inhibition of ET-1 on IKV of PASMCs is partly mediated by BQ123, namely, ETA receptor mediates the effect of ET-1 on IKV of chronic hypoxic PASMCs.     

Effects of simvastatin on transient outward potassium current in ventricular myocytes of normocholesterolemic rabbits suffering from ischemia and reperfusion

AIM: To investigate the effects of simvastatin on transient outward potassium current (Ito) in left ventricular myocytes of rabbit heart undergoing ischemia-reperfusion, so as to explore the cellular (ionic) mechanism of statin treatment for antiarrhythmia. METHODS: Forty-five rabbits were randomly divided into three groups: ischemic-reperfusion group (I-R), simvastatin intervention group (statin) and sham-operation control group (sham). Anesthetized rabbits were subjected to 30 min ischemia by ligation of the left anterior descending coronary artery and 60 min reperfusion after oral administration of simvastatin at dose of 5 mg·kg-1·d-1(statin group) or placebo (I-R group) for 3 d. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region derived from the hearts in I-R, statin group and the same anatomy region in sham. Whole cell patch clamp technique was used to record Ito. Simultaneously, the level of serum cholesterol was examined. RESULTS: No significant difference in serum cholesterol concentration among three groups was observed. The Ito current density (at +60 mV) was significantly decreased in I-R ［(9.49 ±1.91) pA/pF, n=11］ compared with sham ［(17.41± 3.13) pA/pF, n=15, P＜0.01］ and statin ［(15.24 ± 2.41) pA/pF, n=11, P＜0.01］, although there was slight reduction in statin group compared with sham (P＜0.05). CONCLUSION: Ischemia-reperfusion induces significant down-regulation of Ito, which may underlie the altered electrical activity and prolong abnormal transmembrane action potential duration of the surviving ventricular myocytes. Pretreatment with simvastatin attenuates these changes without lowering the serum cholesterol level, suggesting that simvastatin may reverse this electrical remodeling, thus contributing to the ionic mechanism of statin treatment for antiarrhythmia.     

Effect of platelet activating factor on the action potential and potassium currents in guinea-pig ventricular myocytes

AIM: To investigate the effects of platelet activating factor (PAF) on the action potential and potassium currents in guinea-pig ventricular myocytes. METHODS: By using whole-cell patch clamp technique, the effects of PAF on APD₉₀, I_K1 and I_K were investigated in enzymatically dispersed single guinea-pig ventricular myocytes. RESULTS: With 5 mmol/L ATP in the pipette electrode, 1 μmol/L PAF increased APD₉₀ from (225.8±23.3) ms to (352.8±29.8) ms (n=5, P<0.05), decreased I_K1 and I_K tail currents from (-6.1±1.3) nA to (-5.6±1.1) nA (n=5, P<0.05) at -120 mV and from (173.5±16.7) pA to (152.1±11.5) pA (P<0.05, n=4) at +30 mV, respectively. In contract, without ATP in the pipette electrode, 1 μmol/L PAF shortened APD₉₀ from (153.0±24.6) ms to (88.2±19.4) ms (n=5, P<0.01). Incubation of myocytes with 1 μmol/L glibenclamide, a blocker of I_KATP restored prolongation of APD induced by PAF. CONCLUSION: In guinea-pig ventricular myocytes, with 5 mmol/L ATP in the pipette, PAF prolonged APD partly due to the inhibition of I_K and I_K1, while with 0 mmol/L ATP in the pipette, PAF induced an activation of I_KATP, hence a decrease in APD was observed. Therefore, PAF might amplify the heterogeneity between ischemia and normal cardiac myocytes during ischemic reperfusion, which might play a vital role in the pathogenesis of the arrhythmias induced by ischemia/reperfusion.     

Effects of endogenous nitric oxide on potassium channels of bronchial smooth muscle cells from asthmatic rats

AIM: To investigate the effects of in vivo application of L-arginine on potassium channels in bronchial smooth muscle cells (BSMC) isolated from asthmatic model rats. METHODS: Male SD rats were randomly divided into control group, asthmatic group and asthmatic rats treated with L-arginine (L-Arg group). Single BSMCs were obtained by acute enzyme separation method. The resting membrane potential (Em), Ca2+-activated K+ channels (BKCa) currents and voltage-dependent K+ channel (Kv) currents in BSMCs were recorded under whole-cell patch clamp technique. RESULTS: (1) The Em of asthmatic group was significantly lower than that in control group (P<0.05). In vivo application of L-Arg significantly hyperpolarized BSMCs near to control group (P>0.05). (2) The peak current density at +50 mV of KCa: IKca in asthmatic group ［(43.8±16.5) pA/pF］ was significantly lower than that in normal group ［(72.5±19.9) pA/pF］ (P<0.01). Treatment with 300 mg/kg L-Arg significantly increased IKca in asthmatic group to (58.7±12.4) pA/pF (P<0.05). (3) The peak currents density at +50 mV of Kv: IKv in asthmatic group ［(32.4±8.7) pA/pF］ was significantly lower than that in control group ［(57.7±9.8) pA/pF］ (P<0.01). Treatment with L-Arg also significantly increased IKv in asthmatic group to (43.6±7.9) pA/pF, (P<0.05). CONCLUSION: Endogenous NO improves Em in asthmatic BSMCs, increases the activities of BKCa channels and Kv channel. These findings implicate that NO may have a potential therapeutically role in airway hypersensitivity.     

Electrical heterogeneity of transient outward current in thyroxine induced ventricular myocytes of cardiomyopathy rat

AIM: To study the electrical heterogeneity of transient outward potassium current (Ito) in left and right ventricular myocytes of cardiomyopathy rat. METHODS: The rats were peritoneally injected with L-thyroxine 0.5 mg/kg for 10 d to establish the model of ventricular hypertrophy. The right and left ventricular parts of the heart were separated and the ventricular myocytes were prepared by step digestion using enzyme solution. Ito was recorded by using whole cell patch clamp technique. The change of the electrical heterogeneity was determined. RESULTS: The electrical heterogeneity of Ito existed in the normal myocytes of left and right ventricles. In the myocytes of left and right ventricles isolated from the cardiomyopathy rats, the electrical heterogeneity was enhanced obviously and showed statistical difference. At +40 mV depolarizing test potential, the current density of Ito in the myocytes of right ventricle was increased from (9.23±0.84) pA/pF to (11.19±1.73) pA/pF, while the current density of Ito in the myocytes of left ventricle was decreased from (6.99±1.14) pA/pF to (4.95 ±1.84) pA/pF and the dispersion was increased. The V1/2 of right ventricle steady inactivation was increased significantly ［from (-68.85±1.37) mV to (-49.86±0.69) mV］. The time constant τ of de-inactivation changed significantly ［τleft=(79.16±7.04) ms,τright=(53.19±3.72) ms］. CONCLUSION: Enhanced electrical heterogeneity of Ito in the left and right ventricular myocytes of cardiomyopathy rat may represent one of the important ionic mechanisms for some arrhythmia caused by myocardial hypertrophy.     

Blunted response of L-type calcium current to simulated ischemia and reperfusion in ventricular myocytes from diabetic rabbits

AIM: To evaluate the effects of simulated acute ischemia and reperfusion on L-type calcium current (I_{Ca, L}) in ventricular myocytes from diabetic and non-diabetic rabbits.METHODS: Using whole-cell patch clamp techniques, I_{Ca, L} was measured in left ventricular myocytes isolated from 6-week alloxan-induced diabetic rabbits and age-matched control ones at baseline, 5 min of simulated ischemia, and 5 min of reperfusion.RESULTS: There were no significant differences on baseline maximum I_{Ca, L} densities between diabetic and control ventricular myocytes. In control cells (n=11), maximal I_{Ca, L} densities of baseline, ischemia and reperfusion were (-8.36±1.63)pA/pF, (-5.90±1.75)pA/pF and (-4.22±1.02)pA/pF, respectively. The I_{Ca, L} of ischemia was less than that of baseline (P<0.01), while the I_{Ca, L} of reperfusion was less than those of baseline (P<0.01) and ischemia (P<0.05). In diabetic cells (n=9), the I_{Ca, L} of baseline, ischemia and reperfusion were (-7.55±1.62)pA/pF, (-6.05±1.58)pA/pF and (-5.12±1.13)pA/pF, respectively. Only I_{Ca, L} of reperfusion was less than that of baseline (P<0.01), while I_{Ca, L} of ischemia was not significantly different from that of baseline (P>0.05) or reperfusion (P>0.05).CONCLUSION: I_{Ca, L} in diabetic ventricular myocytes represents blunted response to acute ischemic injury, being decreased more slowly than that in control cells. Post-ischemic reperfusion is still a potent inhibitor against I_{Ca, L} in both diabetic and non-diabetic cells. This study may be indicative of the mechanism about ischemia-reperfusion injury to diabetic myocardium and the therapy for diabetic patients with ischemic heart disease.     

Effect of hypoxia on persistent sodium current in ventricular myocytes from 3-week infarcted rat heart

AIM: To investigate the effect of hypoxia on persistent sodium current (INap) in single ventricular myocyte isolated from acute myocardial infarction (AMI) heart of rats and to study the mechanisms of cardiac arrhythmias that occur after AMI. METHODS: AMI model was induced by ligating the left anterior descending coronary artery in rats. The whole-cell patch clamp technique was used to record the current in epicardial myocytes in infarcted region from rats at 3 week after AMI. RESULTS: In normoxic conditions, the current density of INap in cardiomyocytes of fake operation (FO) and AMI hearts was 0.144±0.022 pA/pF (n=9), 0.121±0.013 pA/pF (n=9，P<0.01)， respectively, which was blocked by tetrodotoxin (TTX). The amplitude of INap was gradually increased with the prolongation of hypoxia time, but the increase in extent of INap in FO cells was significant bigger than that in AMI cells. The INap was blocked by 1 mmol/L glutathione. CONCLUSIONS: After AMI, the amplitude of INaP in infarcted and noninfarcted myocardium showed differences both in normoxic and hypoxic conditions, which increased dispersion of repolarization. This may be one of the reasons of reentrant ventricular arrhythmias that occur after AMI.     

Characteristics of pacemaker current in aged rat atrial myocytes

AIM: To investigate the characteristics of pacemker current (I_f) of atrium myocytes in aged rats. METHODS: Aged SD rats (22-24 months) were used in the study. The single atrium myocytes were isolated. I_f current was recorded by the technique of whole-cell patch clamp. RESULTS: The densities of I_f increased markedly in aged rat atrium myocytes compared with that in the cells of young rats. At the test potential of-150 mV, the average amplitude of I_f was (382±23)pA and the current density was (3.2±0.4)pA/pF, while the average amplitude of I_f in control group was (86.9±8.4)pA and the current density was (0.9±0.1)pA/pF,P<0.01. I_f current was augmented at negative hyperpolarzing test potential. Time constants of activation in aged and control cells were (230.2±14.4)ms and (670.5±23.6)ms, respectively. Furthermore, steady state curves in the elder cells was shifted to positive potentials and the voltages for half maximal activation were (-87.2±2.3)mV (aged cells) and (-104.4±6.3)mV (control cells). In contrast, the slope of activation curves and reversed potential of I_f were slightly different between aged cells and control cells. CONCLUSION: The amplitude and densities of I_f in atrium cells of aged rats were larger than that of control rats.     

Effect of experimental acute necrotizing pancreatitis on sodium and L-type calcium current in rat cardiomyocytes

AIM: To study the effect of experimental acute necrotizing pancreatitis (ANP) on sodium and L-type calcium current in rat cardiomyocytes. METHODS: I_Na and I_Ca-L were recorded using whole cell patch-clamp techniques from left ventricular myocytes in ANP model established by retrograde injection of 3.5% sodium taurocholate 2.5 mL/kg into pancreatic duct. RESULTS: Peak I_Na current density (at -30 mV) was significantly reduced in ANP [(12.45±2.26)pA/pF,n=16] compared with sham [(25.32±3.31)pA/pF,n=14], P<0.01; I_Ca-L current density (at +10 mV) was also significantly reduced in ANP [(3.63±0.65)pA/pF,n=16] compared with sham [(5.46±1.03)pA/pF,n=12], P<0.05. CONCLUSIONS: There were changes in both I_Na and I_Ca-L in cardiomyocytes of ANP. These changes may underlie the altered excitability and abnormally short transmembrane action potentials and repolarization of cardiomyocytes, thus contributing to arrhymias in ANP.     

Effects of stretch on transient outward potassium and inward rectifier potassium current in cultured neonatal rat atrial myocytes

AIM：To investigate the effects of mechanical stretch on transient outward potassium current (Ito), inward rectifier potassium current (IK1) and action potential duration(APD) of cultured neonatal rat atrial myocytes. METHODS：Neonatal rat atrial myocytes were isolated and cultured on silicone sheeting with or without stretch for 24 h. The silicone membrane area was increased by 12% in stretched group. The cells without stretch served as control. Ito, IK1 and APD were recorded by the technique of whole-cell patch clamp. RESULTS：Compared with control group, Ito density in stretched myocytes was significantly reduced ［(16±04) pA/pF vs (121±29) pA/pF, P<001］, whereas IK1 density was increased ［(-108±08) pA/pF vs (-88±09) pA/pF, P<001］. The APDs at 50% and 90% levels of repolarization (APD50 and APD90) in the stretched cells were obviously decreased than those in non-stretched cells ［(105±14) ms vs (155±24) ms, (300±28) ms vs (563±36) ms, P<001］. CONCLUSION：Stretch stimulation leads to the reduction of Ito density, the increase in IK1 density and the shortness of APD in cultured rat atrial neonatal myocytes, which may contribute to atrial electrical remodeling induced by pressure overload.     

Effect of cGMP on voltage-gated potassium channel in pulmonary artery smooth muscle cells from rats exposed to chronic hypoxia

AIM: To investigate the effect of cGMP on voltage-gated potassium channel in pulmonary artery smooth muscle cells (PASMCs) from rats exposed to chronic hypoxia. METHODS: (1) Wistar rats were randomly divided into control group (group A) and chronic hypoxia group (group B). Then group B received hypoxia 8 hours per day for 4 consecutive weeks. (2) Single PASMC was obtained via acute enzyme separation method. (3) Conventional whole-cell patch clamp technique was used to record resting membrane potential (Em) and ion currents of voltage-gated potassium channel. The changes of ion currents of voltage-gated potassium channel before and after applying cGMP (1 mmol/L), an agonist of protein kinase G (PKG), and cGMP plus H-8 (1 mmol/L), an inhibitor of PKG were compared between two groups. RESULTS: The Em of group B were significantly lower than that of group A. The ion currents of voltage-gated potassium channel in group A and group B were all significantly inhibited by cGMP [control group: from (118.0±5.0) pA/pF to (89.9±16.5) pA/pF, n=6, P＜0.05;chronic hypoxia group: from (81.0±5.0) pA/pF to (56.8±9.1) pA/pF, n=6, P＜0.05]and these effects were reversed by H-8 [control group: from (119.2±10.3) pA/pF to (117.8±9.1) pA/pF, n=6, P＞0.05;chronic hypoxia group: from (96.8±6.2)　pA/pF to (98.0±2.2)　pA/pF, n=6, P＞0.05]. CONCLUSIONS: The currents of voltage-gated potassium channel was inhibited by chronic hypoxic. The inhibitory effect of cGMP on currents of voltage-gated potassium channel in PASMCs from both normal and chronic hypoxic rats may be probably through the phosphorylation of voltage-gated potassium channel.     

Cardiac IKs as repolarization reserve plays a role in gender difference of diabetic QT prolongation

AIM: To explore the basic ionic mechanisms underlying long-QT syndrome by observing the changes of slowly activating outward rectifying potassium current (I_Ks) and its proteins in abnormal QT prolongation in different genders of diabetic rabbits.METHODS: A single injection of pre-warmed (37 ℃) alloxan (140 mg/kg) was used to establish a rabbit model of insulin-dependent diabetes mellitus. Eight weeks after alloxan injection, the levels of blood glucose in the rabbits were monitored and standard lead II electrocardiogram was recorded. The myocardial cells were isolated from the ventricle of the rabbits via enzymatic digestion. Whole-cell patch clamp technique was performed to study the action potential duration (APD) and I_Ks. The changes of both KvLQT1 and mink proteins were detected by Western blotting analysis.RESULTS: The QT interval and APD were prolonged apparently both in male and female diabetic rabbits. The increased APD/QT-I of the male diabetic rabbits is more remarkable than that of the female. The I_Ks step current density of the male diabetic rabbits was decreased at test potentials ranging from+40 mV to+70 mV compared with that of the control animals (P<0.05), which was lowered from (3.08±0.67) pA/pF (n=17) to (1.27±0.20) pA/pF (n=16) at+70 mV. However, the I_Ks step current density of the female diabetic rabbits was increased at test potentials ranging from 0 mV to+70 mV compared with that of control group (P<0.05), which was increased from (1.56±0.20) pA/pF (n=13) to (3.65±0.50) pA/PF (n=14) at+70 mV. The expression of KvLQT1 and mink in male diabetic group decreased by 21.6% and 18.5%, respectively. However, the expression of KvLQT1 and mink in female diabetic group were increased by 42.3% and 20.5%, respectively.CONCLUSION: The I_Ks may be a protective factor in the early period of diabetic development in female rabbits. As a repolarization reserve, cardiac I_Ks is likely to restrict the effects of excessively slowing repolarization.     

Changes of potassium currents in rabbit ventricle with healed myocardial infarction

AIM: To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), and to investigate the changes of action potential duration (APD),transient outward potassium current (I_to), delayed rectifier potassium current (I_K) and inward rectifier potassium current (I_K1) of left ventricular myocytes in noninfarcted zone of HMI. METHODS: 12 rabbits were randomly assigned in two groups: HMI group (thoracotomy and ligation of the circumflex coronary); sham-operated group (thoracotomy but no conorary ligation). 3 months after operation, whole cell patch clamp technique was used to record APD, I_to, I_K and I_K1 of ventricular myocytes in non-infarcted zone. RESULTS: Membrane capacitance was larger in HMI group than that in sham-operated group. Action potential duration was lengthened significantly in HMI group and early after depolarization (EAD) appeared in HMI group. The densities of I_to, I_K,tail and I_K1 were reduced significantly in HMI group (P<0.01), from (6.72±0.42) pA/pF, (1.54±0.13) pA/pF and (25.6±2.6) pA/pF in Sham-operated group to (4.03±0.33) pA/pF, (1.14±0.11) pA/pF and (17.6±2.3) pA/pF, respectively. CONCLUSION: The reduced densities of I_to, I_K,tail and I_K1 in ventricular myocytes of non-infarcted zone in HMI are responsible for the prolongation of APD and the presentation of EAD, which play important roles in the malignant arrhythmia of HMI.     

Effect of hydrogen sulfide donor on oxidative stress of myocardium in adriamycin-induced dilated cardiomyopathy rats

AIM: To investigate the effect of hydrogen sulfide (H2S) donor (NAHS) on oxidative stress of adriamycin-induced dilated cardiomyopathy rats. METHODS: Weight-matched adult male Wistar rats were randomly divided into 5 groups as follows: (1) ADR group (n=12), in which 2.5 mg/kg of adriamycin was injected intraperitoneally once a week for 10 weeks (total dose of 25 mg/kg). (2) ADR+small-dose NaHS group (n=12), in which the dosage and the use of adriamycin were as mentioned above, while NaHS solution was injected to rats at a dosage of 2.8 μmol·kg-1·d-1 at the same time. (3) ADR + large-dose NaHS group (n=12), in which the dosage and the use of adriamycin were as mentioned above, while NaHS solution was injected to rats at a dosage of 14 μmol·kg-1·d-1 at the same time. (4) Control group (n=9), in which an equivalent volume of physiological saline was administered weekly for a total of 10 weeks. (5) NaHS group (n=9), in which 14 μmol/kg of NaHS solution was injected to rats intraperitonealy once a week for 10 weeks. Hemodynamic and echocardiographic measurements were obtained 10 weeks after the treatment. Meanwhile, H2S and malondialdehyde (MDA) concentrations, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum and myocardial tissues were evaluated, respectively. RESULTS: The cardiac functions in the group of ADR rats depressed obviously. H2S concentrations, SOD and GSH-Px activities in serum and myocardial tissues of ADR group rats were all significantly decreased as compared with those in the control group (P<0.01). The MDA concentrations in serum and myocardial tissues in ADR group rats were both increased significantly (P<0.01). Exogenous administration of H2S donor NaHS markedly attenuated ADR-induced cardiac dysfunction, and MDA concentration in myocardial tissues was significantly reduced (P<0.01). Serum SOD activity was obviously increased in ADR+large-dose NaHS group compared with control group (P<0.01), and GSH-Px activity in myocardial tissues was markedly increased in ADR+large-dose NaHS group compared with control group (P<0.05). CONCLUSION: H2S might play an important role in the development of adriamycin-induced dilated cardiomyopathy. Administration of exogenous H2S effectively improves myocardial contractile activity, reduces the accumulation of lipid peroxides and increases the capability of antioxidants to inhibit oxidative stress and prevents myocardial damage.     

Studies of potassium channel in pulmonary artery smooth muscle cells of pulmonary hypertension rats

AIM：In this work,we investigated the difference of membrane capacitance,membrane current,current density and I-V curves between smooth muscle cells isolated from pulmonary hypertension rat (PHR) or normotensive rat (NTR) pulmonary arteries.METHODS：Thirty young male Sprague-Dawley rats,aged 8-9 weeks,were used.Body weight was (200±20)g at the start of experiments.These rats were placed into a normobaric chamber for 6 h·day-1,6 day·week-1 for 4 weeks.Hypoxic exposure was accomplished by ventilation with room air and N2 resulting in a constant O2 concentration of (10±0.5)%.Whole cell recordings were made from smooth muscle cells freshly isolated from pulmonary arteries derived from PHR or NTR.RESULTS：The membrane capacitance of pulmonary hypertension rats was larger than that in SD rats;but membrane current and current density were lower than those in SD rats (P<0.05).The I-V curves of pulmonary hypertension rat were downward shift compared with that in SD rat.Iptakalim hydrochloride 10 μmol·L-1 significantly increased potassium currents.CONCLUSIONS：Membrane capacitance,membrane current,membrane potential are decreased,I-V curves was shift downward,compared with NTR.Iptakalim hydrochloride significantly increased NTR and PHR potassium currents.     

Valsartan protects a rat model of adriamycin-induced dilated cardiomyopathy from left ventricular remodeling and failure

AIM: To investigate whether and how AT1 receptor blocker， valsartan， attenuates left ventricular remodeling and failure in a rat model of adriamycin（ADR）-induced dilated cardiomyopathy. METHODS: Weight-matched adult male Wistar rats were randomly divided into 3 groups as follows: 1) the ADR group, in which 2.5 mg/kg of ADR was weekly injected via a tail vein for 10 weeks (n=25); 2) concomitant AT1 receptor blocker valsartan and ADR, in which valsartan was administered by daily gavage at a dose of 30 mg·kg-1·d-1 (n=10); 3) control group (n=10). Hemodynamics and echocardiographic measurements were obtained at 12 weeks after treatment. Finally, left ventricle (LV) samples were collected at 12 weeks. The hydroxyproline content was determined by the methods of chloramines T. The expression of MMP-2, MMP-9 and tissue inhibitors of metalloproteinase-1 (TIMP-1) were measured by Western blotting. MMP-2 and -9 gelatinolytic activities were measured by gelatin zymography. RESULTS: Mortality was significantly lower in valsartan -treated rats than that in ADR rats (20% versus 40%, P<0.01). The dilatation of LV cavity was significantly attenuated in ADR-induced dilated cardiomyopathy rats given valsartan. Valsartan partially normalized LV contractile function, which was significantly reduced in ADR rats. The hydroxyproline content was increased in ADR-DCM group and significantly reduced by valsartan treatment (P<0.01). The protein levels of LV MMP-2 and MMP-9 were increased in ADR rats and attenuated by valsartan treatment (both P<0.01). However, no change in TIMP-1 was observed (P>0.05). The activities of LV myocardial MMP-2 and -9 gelatinolytic were increased significantly in ADR rats (both P<0.01) and attenuated by valsartan treatment (both P<0.01). CONCLUSION: Pretreatment with AT1 receptor blocker valsartan attenuates left ventricular remodeling and failure in a rat model of adriamycin-induced dilated cardiomyopathy.     

Activity of delayed rectifier potassium channel in alveolar macrophages from COPD rats

AIM: To explore the change of delayed rectifier potassium channel (KV) activity in alveolar macrophages (AM) in chronic obstructive pulmonary disease (COPD) rats. METHODS: COPD model was established by exposure of the animals to cigarette smoke. With whole-cell voltage- or current-clamp techniques, KV activity, membrane capacitance and resting membrane potential (Em) in AM from COPD model and control rats were compared. RESULTS: (1) Significant increases in total mononuclear cells and AM in bronchoal aveolar lavage fluid (BALF) were found in COPD group compared with in control group. (2) The AM KV current altitude in COPD group ［(520.5±38.7）pA， +50 mV, n=30］ was significantly lower than that in control group ［(713.6±44.4）pA， +50 mV, n=30， P<0.01］; (3) AM from COPD group had no significantly different capacitances (P>0.05), but had more positive Em (P<0.01) compared with those from control group. CONCLUSION: Inhibition of KV function, increase in excitability and more positive Em in AM from COPD rats may be involved in the AM contribution to the COPD development.     

Characteristics of transient outward potassium current in repolarization 1 phase from the canine right ventricular mid-myocardial cells

AIM: To examine the electrophysiological characteristics of transient outward potassium current(Ito₁) in repolarization 1 phase from the canine right ventricular M cells. METHODS: By use of whole cell patch-clamp technique, we quantitatively researched the ionic intensity, density of Ito₁ and the notch magnitude of action potential in repolarization 1 phase. RESULTS: (1) The activating process of Ito₁ of canine right ventricular M cells presented evident voltage-dependency. Under the condition of 37℃, 5 000 ms, 0 mV and +70 mV, the average peak Ito₁ intensity of right ventricular M cell were (690±380) pA and (3 130±1 910) pA, respectively (P＜0.01). (2) The Ito₁ intensity of canine right ventricular M cell possessed obvious frequent dependency. Under the condition of 37℃,+70 mV, 500 ms and 5 000 ms, the average peak Ito₁ intensity were (1 690±830) pA,(3 130±1 910) pA, respectively(P＜0.01), corresponding to the increase of action potential "spike-dome" magnitude in repolarization 1 phase. CONCLUSION: Potent Ito₁ as well as the "spike-dome"-like action potential figure mediated by Ito₁ is one of the prominent electrophysiological characteristics of the canine right ventricular M cells.