Effects of total flavones of Elsholtzia splendens in isolated ischemia/reperfusion rat hearts / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the influence of total flavonoids of Elsholtzia splendens (TFES) on isolated ischemia/reperfusion rat hearts and its underlying mechanisms.</p><p><b>METHODS</b>Hearts isolated from male SD rats were perfused on the Langendorff apparatus and subjected to global ischemia for 30 min followed by 120 min of reperfusion. The cardiac infarct size was measured by TTC staining. Hemodynamic parameters and the level of lactate dehydrogenase (LDH) in the coronary effluent were measured. Absorbance at 520 nm was determined in isolated cardiac mitochondria exposed to 200 micromol/L CaCl2 to detect the opening of the mitochondrial permeability transition pore.</p><p><b>RESULTS</b>Pretreatment with TFES (1, 10, 100 microg/ml) for 5 min decreased infarct size and LDH release and improved the recovery of the left ventricular developed pressure. In mitochondria, the decrease of absorbance at 520 nm evoked by CaCl2 was greatly inhibited by TFES.</p><p><b>CONCLUSION</b>TFES prevents myocardial ischemia/reperfusion injury, and this cardioprotective effect is probably via inhibiting mitochondrial permeability transition pore opening.</p>

Effect of S-allyl-L-cysteine on isolate heart subject to ischemia/reperfusion / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effect of S-allyl-L-cysteine (SAC) on isolated rat heart subject to ischemia/reperfusion(I/R) injury and the mechanisms.</p><p><b>METHODS</b>The isolated perfused rat hearts on a Langendorff apparatus were subjected to global ischemia for 30 min and followed by 120 min of reperfusion. Hemodynamic index, the production of formazan and the level of lactate dehydrogenase (LDH) in the coronary effluent were determined. Superoxide dismutase (SOD) and reactive oxygen species (ROS) in myocardial homogenates were measured.</p><p><b>RESULTS</b>Compared with I/R group, the hemodynamics were greatly improved, the production of formazan was increased, and LDH level in effluent was reduced in SAC group. SAC improved the SOD activity and significantly decreased the level of ROS. In addition, threonine (Thr) attenuated the protective effect of SAC significantly.</p><p><b>CONCLUSION</b>SAC has protective effect against myocardial ischemia/reperfusion injury on rats. The possible mechanism is that SAC be transported into the cell through alanine-serine-cysteine-transporter 1 (ASCT-1) improves SOD activity and reduces the level of ROS.</p>

Expression and function of autophagy after ischemia/reperfusion in rats hippocampus neuron / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the expression of autophagy after ischemia/reperfusion and its possible function in rats hippocampus neurons.</p><p><b>METHODS</b>After 2 hours oxygen-glucose deprivation and different periods time of reperfusion (OGD/R) treatment in primary hippocampal neurons, neuron viability was evaluated by MTT assay, specific structure of autophagosome and specific protein of autophagy microtubule-associated protein 1 light chain 3 B (LC3B) were detected by transmission electron microscope and immunofluorescence respectively. The inhibitor of autophagy 3-Methyladenine (3-MA) was also used to exam the viability of neurons.</p><p><b>RESULTS</b>Treatment by OGD/R markedly reduced neuronal viability. Compared to the control group, autophagy existed in different time periods after OGD/R shown both in transmission electron microscope and immunofluorescence. Application of 3-MA significantly reduced neuronal viability.</p><p><b>CONCLUSION</b>Oxygen-glucose deprivation can activate autophagy in rat hippocampus neurons, which may resist the injury during ischemia/reperfusion.</p>

Luteolin reduces cardiac dysfunctions in streptozotocin-induced diabetic rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effects of luteolin (Chinese Traditional Medicine) on cardiac functions and mitochondrial oxidative stress in streptozotocin (STZ)-induced diabetic rats.</p><p><b>METHODS</b>Male SD rats were randomly divided into a normal control group, a luteolin control group, a diabetic group, and diabetic groups orally administered with a low dose (10 mg/(kg x d)) or a high dose of luteolin (100 mg/ (kg x d)) for eight weeks. The body weight, blood glucose, cardiac functions, left ventricular weight, myocardial collagen and reactive oxygen species (ROS) levels were assayed. The cardiac mitochondrial ROS level, superoxide dismutase (SOD) activity and the mitochondrial swelling were measured.</p><p><b>RESULTS</b>Treatment with luteolin had no effect on the blood glucose but reduced the losing of body weight in diabetic rats. High dose of luteolin markedly reduced the ratio of ventricular weight and body weight, increased the left ventricular develop pressure, and decreased the left ventricular end diastolic pressure in diabetic rats. The myocardial levels of ROS and collagen, the cardiac mitochondrial ROS level, and the mitochondrial swelling in diabetic rats were all markedly reduced by high dose of luteolin. Furthermore, high dose of luteolin significantly increased the mitochondrial SOD activity in diabetic rat hearts.</p><p><b>CONCLUSION</b>Treatment with luteolin for 8 weeks markedly improves the cardiac function, which may be related to reducing mitochondrial oxidative stress and mitochondrial swelling in diabetic rats.</p>

Auricularia auricular polysaccharide protects myocardium against ischemia/reperfusion injury / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To determine whether auricularia auricular polysaccharide (AAP) protects heart against ischemia/reperfusion (1/ R) injury and its underlying mechanisms.</p><p><b>METHODS</b>Male Sprague-Dawley rats, pretreated with AAP (50, 100, 200 mg/(kg x d), gastric perfusion) for 4 weeks, were used for Langendorff isolated heart perfusion. The hearts were subjected to global ischemia for 30 min followed by 120 min of reperfusion and the left ventricular hemodynamic parameters were measured. Formazan, a product of 2, 3, 5-triphenyl-tetrazolium chloride (TTC), which is proportional to myocardial viability, was measured at 490 nm, and the level of lactate dehydrogenase (LDH) in the coronary effluent was measured to evaluate the cardiac injury. The cardiac malondialdehyde (MDA), a product of lipid peroxidation, and superoxide dismutase (SOD) activity were determined after myocardial I/R.</p><p><b>RESULTS</b>The pretreatment with AAP at 50, 100, 200/(kg d) for 4 weeks before I/R increased myocardial formazan content, reduced LDH release, improved the recovery of the left ventficular developed pressure, maximal rise rate of left ventricular pressure, and rate pressure product (left ventricular developed pressure multiplied by heart rate) attenuated the decrease of coronary flow during reperfusion. The cardiac protective effect of high dose AAP was more potent than that of compound radix salviae miltiorrhizae (CRSM, 4 ml/(kg x d), gastric perfusion for 4 weeks). Pretreatment with AAP (100 mg/(kg x d)) markedly inhibited the increase of MDA level and the decrease of SOD activity induced by I/R in myocardium.</p><p><b>CONCLUSION</b>The findings indicate that in the isolated rat heart, AAP protects myocardium against ischemia/reperfusion injury via enhancing the activity of SOD and reducing lipid peroxidation in heart.</p>

Myocardial protective effect of acetylcholine against ischemia/reperfusion injury and its underlying mechanism / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To determine whether the caidioprotection of acetylcholine (ACh) against ischeniia/reperftision (I/R) injury is re-kited to mitochondrial permeability transition pore (MEW) and mitochondrial AW-sensitive potassium channel (mitoK(ATP)).</p><p><b>METHODS</b>Male Sprague-Dawley rats were used for Langendorif isolated bean perkision. The hearts were subjected to global ischemia for 30 mm followed by 120 rein of reperfusion and the left ventricular hemodynaniic parameters were measured. Formazan, a product of 2,3, 5-triphenyl-tetrazolium chloride (TTC), which is proportional to myocardial viability, was measured at 490 nm, and the level of lactate dehydrogenase (LDH) in the coronary effluent was measured to evaluate the cardiac injury.</p><p><b>RESULTS</b>The pretreatment with ACh (0.1 mol/L, 5 mm) before I/R markedly increased myocardial formazan content, reduced LDH release, improved the recovery of the left veritficular developed pressure, +/- dP/dtmax, and rate pressure product (left ventricular developed pressure multiplied by hean rate) and attenuated the decrease of coronary flow during reperfusion. The opener of MPTP, atiractyloside (20 mmoL/L) or the inhibitor of mitoK(ATP), 5-hydroxydecanoate (100 micromol/L) abolisbed the beneficial effect of ACh.</p><p><b>CONCLUSION</b>In the isolated rat bean, ACh protects myocardium against ischemia/reperfusion injury via inhibiting the opening of MPTP and increasing the opening of mitoKATP in heart.</p>

Study of the effects of Auricularia auricular polysaccharide on local ischemia/reperfusion injury in rat / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the influence of Auricularia Auricular polysaccharide (APP) on acute cerebral injury induced by ischemia/reperfusion in rats and its underlying mechanism.</p><p><b>METHODS</b>Adult male SD rats were intragastrically pretreated with AAP at a low (50 mg/kg) or high (100 mg/kg) dose once a day for 20 days before operation. Rats intraperitoneally injected with ginkgo biloba extract (EGb671) were taken as positive control. Focal ischemia was achieved by middle cerebral artery occlusion (MCAO) on the right side for 60 min. After 24 hrs of reperfusion, the nerve function defects were recorded by Longa's score and the brain infarct sizes were measured by 2,3,5-Triphenyl-tetrazolium-chlor (TTC) staining. Apoptotic neurons were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining after 48 h of reperfusion. The levels of oxidative stress was determined via the mitochondria-generated reactive oxygen species (ROS).</p><p><b>RESULTS</b>AAP treatment decreased Longa's score, brain infarct size, apoptotic neurons and mitochondria-generated ROS in a dose-dependent manner. AAP at 100 mg/kg gave a better performance compared with EGb671 on all parameters examined.</p><p><b>CONCLUSION</b>AAP treatment protected rat brain from focal ischemia/reperfusion injury by its anti-oxidative effect and worked better than EGb671.</p>

Partial endothelium-dependent vasorelaxation of crocetin and its mechanism / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the vasorelaxation effect of crocetin (CCT) and its mechanism.</p><p><b>METHODS</b>Isolated aortic rings from Sprague-Dawley rats were mounted in the organ bath system. The tension of the aorta was recorded.</p><p><b>RESULT</b>CCT significantly provoked concentration-dependent relaxation in both endothelium-intact and-denuded aortic rings pre-constricted by phenylephrine (10⁻⁵ mol/L), and the vasorelaxation in endothelium-intact aortic rings was stronger than that in endothelium-denuded ones. CCT had no significant effects on aortic rings pre-constricted with KCl (6 × 10⁻² mol/L). Pretreatment with eith L-NAME (10⁻⁴ mol/L), an inhibitor of nitric oxide synthase (NOS), or indomethacin (10⁻⁵ mol/L), an inhibitor of cyclooxygenase, for 30 min significantly attenuated the relaxation of endothelium-intact aortic rings induced by CCT. Besides, both tetraethylammonium (a Ca²(+)-activated K(+) channel inhibitor, 5 × 10⁻³ mol/L) and 4-aminopyridine (a voltage-sensitive K(+) channel inhibitor, 10⁻³ mol/L), but not the ATP-sensitive K(+) channel inhibitor glibenclamide (3 × 10⁻⁶ mol/L), significantly attenuated CCT-induced relaxation in endothelium-denuded aortic rings.</p><p><b>CONCLUSION</b>CCT had partial endothelium-dependent relaxation in rat aortas, which may be mediated by activating the endothelial NOS-NO and cyclooxygenase-prostacyclin pathways. The endothelium-independent relaxation in rat aortas induced by CCT may be mediated by Ca²(+)-activated K(+) channels and voltage-sensitive K(+) channels.</p>

Electrophysiological effect of atorvastatin on isolated rat hearts injured by ischemia/reperfusion / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the myocardial electrophysiological effect and its underlying mechanisms of atorvastatin (Ator) on isolated rat hearts injured by ischemia/reperfusion (I/R).</p><p><b>METHODS</b>Isolated SD rat hearts were mounted on Langendorff system, and a local I/R was induced by ligation (30 min) and release (15 min) of the left anterior descending artery. During the reperfusion period, the effect of Ator on diastolic excitation threshold (DET), effective refractory period (ERP) and ventricular fibrillation threshold (VFT) on rat heart were measured.</p><p><b>RESULT</b>Compared with the control group, medium concentration of Ator prolonged the ERP in normal rat hearts; low, medium and high concentration of Ator significantly inhibited the decrease of DET, ERP and VFT induced by I/R. However, pretreatment with L-NAME cancelled these cardiac electrophysiological effects of Ator.</p><p><b>CONCLUSION</b>Ator reduced electrophysiological alteration induced by I/R in isolated rat hearts, which may be mediated by activating nitric oxide pathway to enhance the myocardial electrophysiological stability.</p>

Effect of gap junction on the cardioprotection of ischemic postconditioning in rat heart / 中国应用生理学杂志

<p><b>AIM</b>To determine whether the cardioprotection of ischemic postconditioning and heptanol in ischemic heart against ischemia/reperfusion (I/R) is mediated by gap junction.</p><p><b>METHODS</b>The effect of ischemic postconditioning, heptanol at different doses (0.03, 0.06, 0.30, and 0.60 mg/kg) and AAP10 (10 mg/kg) on the intact rat heart during 30 min ischemia and 2 h of reperfusion was observed. Ischemic postconditioning was achieved by 3 cycles of 10 s reperfusion/10 s regional ischemia starting at the beginning of the reperfusion. The infarct size and the arrhythmia scores were measured. The effect of ischemic postconditioning, heptanol at different doses (0.05, 0.10, 0.50 and 1.00 mmol/L) and AAP10 (1 x 10(-7)mol/L) on the isolated heart during 30 min ischemia and 2 h of reperfusion was observed. Ischemic postconditioning was achieved by 6 cycles of 10 s reperfusion/10 s global ischemia starting at the beginning of the reperfusion. The arrhythmia scores and conduction velocity of ventricle muscle were measured.</p><p><b>RESULTS</b>In the intact rat heart model, ischemic postconditioning and heptanol reduced infarct size and arrhythmia scores. In the Langendorff perfused rat heart model, ischemic postconditioning and heptanol reduced arrhythmia scores and conduction velocity of ventricle muscle. Administration of AAP10, an opener of gap junction attenuated the cardioprotection of ischemic postconditioning and heptanol.</p><p><b>CONCLUSION</b>The cardioprotection of ischemic postconditioning and heptanol may be related to the attenuation of gap junction communication on myocardiac ischemia/reperfusion injury.</p>

Antiarrhythmic effect of ethyl acetate extract from Chrysanthemum Morifolium Ramat on rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of ethyl acetate extract from Chrysanthemum Morifolium Ramat (CME) on experimental arrhythmia induced by ischemia/reperfusion or aconitine in rats and to explore its underlying mechanisms.</p><p><b>METHODS</b>Arrhythmia model in intact rat was induced by aconitine (30 microg/kg body weight, i.v.). In isolated Langendorff perfused rat hearts, regional ischemia and reperfusion was induced by ligation and release of left anterior descending artery. The ventricular fibrillation threshold (VFT), effective refractory period (ERP), and diastolic excitation threshold (DET) in the isolated heart were measured. The action potentials of papillary muscle in rat right ventricle were recorded by conventional glass microelectrode technique.</p><p><b>RESULTS</b>Compared with control group CME significantly decreased the number and duration of ventricular tachycardia (VT); delayed the occurrence of ventricular premature beats (VPB) and VT induced by aconitine. Arrhythmia score of the CME group was lower than that in aconitine-treated group. CME markedly prolonged the ERP and increased the VFT in the isolated perfused rat hearts during ischemia and reperfusion. CME prolonged action potential duration at 50% and 90% repolarization of the right ventricular papillary muscles and decreased the maximal rate of rise of the action potential upstroke, but did not affect the resting potential, amplitude of action potential.</p><p><b>CONCLUSION</b>CME can reduce myocardial vulnerability and exerts its antiarrhythmic effects induced by aconitine or ischemia/reperfusion, which may be related to its prolongation of action potential duration and effective refractory period that enhance the electrophysiological stability of myocardiaium.</p>

Superoxide anion inhibit endothelium-dependent relaxation in rat mesenteric artery / 中国应用生理学杂志

<p><b>AIM</b>To explore the resistant arterial effect of superoxide anion and its possible mechanisms.</p><p><b>METHODS</b>The third branch of the superior mesenteric artery in male Sprague-Dawley (200-300 g) rats was rapidly excised. Periadventitial fats and connective tissues were removed and the artery was dissected into about 2 mm rings. Each ring was dispensed between two stainless steel wires (diameter 0.0394 mm) in a 5 ml organ bath (DMT 610 M, Danish Myo Technology, Denmark). Isometric force recording studies in vitro of rat mesenteric arterial rings were recorded by Powerlab Syetem. Exposure of arteries to superoxide was accomplished through the auto-oxidation of pyrogallol added to the artery baths. Then endothelium-dependent or independent relaxation was investigated, respectively.</p><p><b>RESULTS</b>Exposure to pyrogallol (10, 100, 300, and 1 000 micromol/L) which could produce superoxide anion for 15 min resulted in a dose-dependent manner in a decrease of acetylcholine(ACh)-induced relaxation in rat mesenteric artery. Especially, the two predominant components of acetylcholine(ACh)-induced endothelium-dependent relaxation, EDHF component and NO component were both inhibited by superoxide anion from pyrogallol. However, exposure to superoxide anion from pyrogallol had no effect on the endothelium-independent relaxations to pinacidil or sodium nitroprusside (SNP) in rat mesenteric artery.</p><p><b>CONCLUSION</b>These results indicate that superoxide anion can inhibit the endothelium-dependent relaxation in rat mesenteric artery, but has no effect on the endothelium-independent relaxation, in which the inhibited effect of EDHF and NO from endothelium is involved.</p>

Cardioprotection of mitoSlo1 channel activation involves mitochondrial permeability transition in ischemia and reperfusion of rat hearts / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate whether the cardioprotection of mitochondrial Slo channel (mitoSlo(1) channel) is associated with mitochondrial permeability transition in isolated rat hearts subjected to ischemia and reperfusion.</p><p><b>METHODS</b>Isolated perfused rat hearts were subjected to 30 min regional ischemia (occlusion of left anterior descending artery) and 120 min reperfusion. The infarct size, lactate dehydrogenase (LDH) release during reperfusion and ventricular hemodynamic parameters were measured.</p><p><b>RESULTS</b>Pretreatment with mitoSlo(1) channel opener, NS1619 10 micromol/L for 10 min reduced the infarct size and LDH release, and improved the recovery of left ventricular developed pressure, left ventricular end-diastolic pressure, maximal rise/fall rate of left ventricular pressure and coronary flow during reperfusion. Administration of atractyloside (20 micromol/L), an opener of mitochondrial permeability transition pore, for 20 min (last 5 min of ischemia and first 15 min of reperfusion) attenuated the reduction of infarct size and LDH release and improvement of left ventricular performance induced by NS1619. In the isolated mitochondria, a significant inhibition of Ca(2+)-induced swelling was observed when mitochondria were incubated with NS1619.</p><p><b>CONCLUSION</b>MitoSlo(1) channel activation by NS1619 protects the myocardium against ischemia and reperfusion injury by inhibiting mitochondrial permeability transition pore opening.</p>

Endogenous catecholamine participates in the action of interleukin-2 on the isolated rat heart / 中国应用生理学杂志

<p><b>AIM</b>To explore whether endogenous catecholamine participates in the effect of interleukin-2 on the isolated heart.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>(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.</p><p><b>CONCLUSION</b>Endogenous 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.</p>

Interleukin-2 reduces calcium handling capacity of rat ventricular myocytes during anoxia/reoxygenation / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effect of interleukin-2(IL-2) on the cell contractility and calcium handling in cardiomyocytes during normoxia or anoxia/reoxygenation.</p><p><b>METHODS</b>Chemical anoxia introduced by Krebs-Henseleit(K-H) solution containing 10(-3) mol/L sodium dithionite was used in the enzymatically isolated rat ventricular myocytes. The video-tracking system and spectrofluorometric method were employed to verify the cell contraction and calcium handling of the single myocyte.</p><p><b>RESULTS</b>During anoxia, the cell contraction, amplitude of calcium transient induced by electrical stimulation and Ca2+ release induced by caffeine were depressed while resting calcium level was elevated, but the activity of the L-type calcium channels were not changed. All the parameters could not return to the pre-anoxia level during reoxygenation. IL-2 at 2 x 10(5) U/L administrated during anoxia aggravated the effect of reoxygenation on cell contraction and the calcium handling.</p><p><b>CONCLUSION</b>Coexistence of IL-2 during anoxia aggravated the effect of reoxygenation on the cell contraction and calcium handling in the isolated rat ventricular myocytes, in which the reduced calcium release from sarcoplasmic reticulum was involved.</p>

Role of interleukin-2 in the functional myocardial impairment induced by anoxia and reoxygenation / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of interleukin-2 (IL-2) on myocardial impairment during ischemia/reperfusion or anoxia/reoxygenation.</p><p><b>METHODS</b>Chemical anoxia was introduced in the isolated rat ventricular myocytes by Krebs-Henseleit (K-H) solution containing 10(-3) mol/L sodium dithionite. The video-tracking system and spectrofluorometric method were employed to verify the cell contraction and calcium homeostasis of the single myocyte. Radioimmunoassay was used to analyze the IL-2 levels in myocardium.</p><p><b>RESULTS</b>The levels of IL-2 in myocardium subjected to ischemia/reperfusion were elevated [(14.34+/-5.99 compared with 22.25+/-3.68)ng/g, P<0.01]. During anoxia, cell contraction and the amplitude of electrically induced calcium transient were depressed and the parameters did not return to the pre-anoxia level during reoxygenation. IL-2 at 200 U/L administered during anoxia aggravated the effect of reoxygenation on cell contraction and calcium transient. After perfusion with IL-2, the malondialdehyde content of myocardial mitochondria was elevated.</p><p><b>CONCLUSION</b>Coexistence of IL-2 during anoxia aggravates the effect of reoxygenation on the cell contraction and calcium homeostasis in the isolated rat ventricular myocytes, in which the mitochondrial lipid peroxidation induced by IL-2 is involved.</p>

Interleukin-2 induced endothelium-dependent relaxation of rat thoracic aorta / 生理学报

Interleukin-2 (IL-2) therapy often results in potentially life-threatening side effects including hypotension. However, the mechanism has not been completely elucidated. In order to determine whether IL-2 modifies vascular tone, we investigated the effect of IL-2 on rat thoracic aorta rings and the underlying mechanisms. Effects of IL-2 on the contraction of high KCl and phenylephrine (PE) preconstricted rat thoracic aorta with or without endothelium were determined by organ bath technique. To explore the mechanism, nitric oxide synthase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME), guanylyl cyclase inhibitor methylene blue, and cyclooxygenase inhibitor indomethacin were used. IL-2 (10-1000 U/ml) caused concentration-dependent relaxation of aorta rings preconstricted with PE (10 micromol/L) in endothelium-intact rings, but had no effect on KCl (120 mmol/L) preconstricted rings. Removal of the endothelium, or pretreatment with L-NAME (0.1 mmol/L) or methylene blue (10 micromol/L) or indomethacin (10 micromol/L), inhibited the relaxation of IL-2. The results indicate that the relaxation by IL-2 in rat aorta ring is endothelium-dependent and is possibly mediated by the NO-guanylyl cyclase pathway and cyclooxygenase-dependent pathway.

Effect of interleukin-2 on the activity of Ca2+ ATPase and Na+/K+ ATPase of sarcoplasmic reticulum and sarcolemma / 生理学报

The purpose of the present study was to investigate whether interleukin-2 (IL-2) changes the activity of sarcoplasmic reticulum (SR) Ca(2+) ATPase, sarcolemmal Ca(2+)ATPase and Na(+)/K(+) ATPase by measuring the Pi liberated from ATP hydrolysis with colorimetrical methods. It was shown that the activity of Ca(2+)ATPase in SR from IL-2-perfused (10, 40, 200, 800 U/ml) rat heart increased dose-dependently. After incubation of the SR with ATP (0.1 approximately 4 mmol/L), the activity of SR Ca(2+)ATPase increased dose-dependently in the control group. In the SR from 200 U/ml IL-2-perfused hearts, the activity of Ca(2+)ATPase was much higher than that in the control group. On the other hand, incubation of the SR with Ca(2+) (1 approximately 40 micromol/L) increased the activity of SR Ca(2+) ATPase in the control group. The activity of SR Ca(2+)ATPase of IL-2-perfused hearts was inhibited as the function to Ca(2+). Pretreatment with specific kappa-opioid receptor antagonist nor-BNI (10 nmol/L) for 5 min attenuated the effect of IL-2 (200 U/ml) on the activity of SR Ca(2+) ATPase. After pretreatment with pertussis toxin (PTX, 5 mg/L) or U73122 (5 micromol/L), IL-2 failed to increase SR Ca(2+)ATPase activity. The activity of SR Ca(2+)ATPase was not changed by incubation of SR isolated from normal hearts with IL-2. Perfusion of rat heart with IL-2 did not affect the activity of sarcolemmal Ca(2+)ATPase and Na(+)/K(+)ATPase. It is concluded that perfusion of rat heart with IL-2 increases the activity of SR Ca(2+)ATPase dose-dependently, which is mainly mediated by cardiac kappa-opioid receptor pathway including a PTX sensitive Gi-protein and phospholipase C. IL-2 increases the activity of SR Ca(2+)ATPase as the function to ATP, but inhibits the activity of SR Ca(2+)ATPase as the function to Ca(2+). IL-2 has no effect on the activity of sarcolemmal Ca(2+)ATPase and Na(+)/K(+)ATPase.