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OBJECTIVE: Iptakalim is a putative ATP-sensitive potassium (KATP) channel opener. It is also a novel nicotinic acetylcholine receptor (nAChR) blocker and can antagonize nicotine-induced increase in dopamine release in the nucleus accumbens. Our recent work also shows that iptakalim exhibits a clozapine-like atypical antipsychotic profile, indicating that iptakalim may possess a dual action against nicotine addiction and schizophrenia. METHODS: The present study examined the potential therapeutic effects of iptakalim on nicotine use in schizophrenia. We created an animal model of comorbidity of nicotine addiction and schizophrenia by injecting male Sprague-Dawley rats with nicotine (0.40 mg/kg, subcutaneously[sc]) or saline, in combination with phencyclidine (PCP, 3.0 mg/kg, sc) or saline daily for 14 consecutive days. RESULTS: During the PCP/nicotine sensitization phase, PCP and nicotine independently increased motor activity over time. PCP also disrupted prepulse inhibition (PPI) of acoustic startle response. Acute nicotine treatment attenuated the PCP-induced hyperlocomotion and PCP-induced disruption of PPI, whereas repeated nicotine treatment potentiated these effects. Importantly, pretreatment with iptakalim (10-20 mg/kg, intraperitoneally) reduced nicotine-induced hyperlocomotion in a dose-dependent fashion. This reduction effect was highly selective: it was more effective in rats previously sensitized to the combination of PCP and nicotine, but less effective in rats sensitized to saline, nicotine alone or PCP alone. CONCLUSION: To the extent that the combined nicotine and PCP sensitization mimics comorbid nicotine addiction in schizophrenia, the preferential inhibitory effect of iptakalim on nicotine-induced hyperlocomotion suggests that iptakalim may be a potential useful drug for the treatment nicotine abuse in schizophrenia.
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Animals , Humans , Male , Rats , Acoustics , Comorbidity , Dopamine , Models, Animal , Motor Activity , Nicotine , Nucleus Accumbens , Phencyclidine , Potassium , Propylamines , Psychotic Disorders , Rats, Sprague-Dawley , Receptors, Nicotinic , SchizophreniaABSTRACT
Objective: To observe the effects of iptakalim on renal injury induced by lipopolysaccharide (LPS), oleic acid and diethylene glycol(DEG). Methods: By njection of 2% ead acetate and 1 μg (1 ml/kg) LPS to rats' femoral vein, 4 h later the experimental models of renal injury induced by LPS have been developed. By injection of 0.15 ml/kg oleic acid to rats' left renal artery, 24h later the experimental models of renal injury induced by oleic acid have been developed. Iptakalim was orally gavaged at the doses of 1,3,9 mg/(kg · d) for 3 d and 1 h before injury. The experimental models of renal injury have been developed by injection of DEG 10 g/kg to mice's peritoneal cavity, then iptakalim was orally gavaged at the doses of 1,3,9 mg/(kg·d) for 6 d. After the experimental models have been set up, observe the serum levels of creatinine(Cr), blood urea nitrogen(BUN) and pathological changes in renal tissue, for the further evaluation of renal function. Results: (1) In rats with the shock induced by LPS, significantly increased serum evels of Cr and BUN were found. Renal cortex of injury rats showed obviously glomerulus microthrombi, tubular cell swelling, necrosis, congestion and cast. Pretreatment of iptakalim at the dose of 9 mg/kg showed improved renal dysfunction and pathological changes in renal tissue. (2) In rats with the renal injury induced by oleic acid, significantly increased serum levels of Cr and BUN were found. Renal cortex of renal injury rats showed obviously glomerulus endothelial cell necrosis, tubular cell congestion and cell cast. Iptakalim had no effect on damaged renal function and the morphological changes in renal tissue. (3) In mice with the renal injury induced by 10 g/kg of DEG, significantly increased serum evels of Cr were found. Iptakalim at the doses of 9 mg/kg decreased serum evels of Cr to normal level. Conclusion: Iptakalim does not fit for individuals of renal damage caused by LPS or oleic acid. The protective effects of iptakalim against renal damaged by DEG need to be further investigated.
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Aim To investigate the effects of iptakalim(IPT),a novel K_(ATP) opener,on the functions of endothelin system in human pulmonary artery endothelial cells.Methods Primary cultured human pulmonary artery endothelial cells were incubated with different concentrations iptakalim for 24 h.The levels of ET-1 in medium were observed by radioimmunoassay.Reverse transcription polymerase chain reaction(RT-PCR)was performed to analyze the expression of ET-1 and ECE.Results When endothelial cells were incubated with IPT at concentrations above 10 μmol·L~(-1),the levels of ET-1 release in medium and the levels of ET-1 mRNA were significantly inhibited.When endothelial cells were incubated with IPT at concentrations above 1 μmol·L~(-1),the levels of ECE mRNA were significantly inhibited.Conclusions IPT can inhibit the expression of ET-1 and ECE mRNA from human pulmonary artery endothelial cells, thus it inhibits the secretion of ET-1 from endothelial cells. Iptakalim may serve as a promising candidate drug to treat pulmonary hypertension.
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Aim To study mRNA and protein expression of eNOS in pulmonary tissue of chronic hypoxic pulmonary hypertension(HPH)rats and chronic hypoxic rats treated with novel KATP opener iptakalim.Methods sixty Sprague-Dawley(SD)male rats were randomly divided into control group, hypoxic group, low dose iptakalim group(0.75 mg·kg~(-1)·d~(-1)), and high dose iptakalim group(1.5 mg·kg~(-1)·d~(-1)).Except the first group, the other three groups were put into hypoxic and normobaric chamber (10%±0.5% O_2,8 h/day and 6 day/week) to establish chronic hypoxic model. After four weeks, the mean pulmonary arterial pressure(mPAP), RV/(LV+S)and the plasma concentration of NO were measured. RT-PCR was performed to analyze the mRNA expression of eNOS in pulmonary tissue. Western blot was performed to analyze the protein expression of eNOS, iNOS in pulmonary tissue. Results ① The level of mPAP and RV/ ( LV + S) were significantly higher in the hypoxic group than those in control group ( P < 0. 05 ) , Low dose iptakalim groupandhighdoseiptakalimgroupdecreased the level of mPAP and RV/( LV + S) significantly (P <0. 05). ② The level of NO was significantly lower in the hypoxic group than those in control group (P<0. 05). Low dose iptakalim group and high dose iptakalim group increased the level of NO significantly (P < 0. 05 ). ③ The mRNA and protein expression of eNOS in the hypoxic group were significantly lower than those in the control group (P < 0. 05 ). Low dose iptakalim group and high dose iptakalim group increased the expression of eNOS significantly ( P < 0. 05). High dose iptakalim group was more significant. Conclusion Pulmonary vascular endothelial dysfunction is induced by chronic hypoxia,and the level of NO, the mRNA and protein expression of eNOS are decreased. Iptakalim can improve the vascular endothelial dysfunction, increase the expression of eNOS and the level of NO and reverse hypoxic pulmonary hypertension.
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Objective To investigate the preventive effect of iptakalim hydrochloride(Ipt) on brain edema in rats after exposure to simulated high altitude and the mechanisms involved.Method Adult Wistar rats were randomly divided into normoxic control group,simulated plateau acute hypoxia group simulated 8 000 m for 8 h and three Ipt taking groups which were pretreated with 2, 4 and 8 mg(kg?d) of Ipt respectively for 7d before exposure to hypoxia.Water content was determined by the wet-dry method;Na~+,K~+,Ca~(2+) and Mg~(2+) content in the cortex was detected with all atomic absorption spectrophotometer;inorganic phosphorus standardization was applied to decide the activities of Na~+/K~+-ATPase,Ca~(2+)-ATPase and Mg~(2+)-ATPase;Occludin and AQP4 gene expression were determined by RT-PCR.Result The water content was increased and the concentration of Na~+ and Ca~(2+),the activities of Na~+/K~+-ATPase,Ca~(2+)-ATPase and Mg~(2+)-ATPase and the gene expression of the Occludin and AQP4 were all down-regulated in acute hypoxia group compared with normoxic control group.And these changes could be significantly relieved by pretreatment with Ipt.Conclusion Ipt can prevent the occurrence of brain edema caused by acute hypobaric hypoxia possibly related to the effect on water content,electrolytes concentration,ATPase activity and gene expressions of aquaporin and tight junction proteins.
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Aim: To investigate the effects of iptakalim hydrochloride (Ipt), a new antihypertensive drug, on the functions of endothelin system. Methods: Radioimmunoassay was used to test the plasma endothelin (ET) concentration of rats and endothelin released from cultured vasocular endothelial cells. The expressions of ET and endothelin converting enzyme (ECE) were determined by RT-PCR. The effects of endothelin on vascular tone were studied in isolated rat aorta. The pulmonary artery pressure was measured in anaesthetized rats. Results: Circled digit one In stroke-prone spontaneously hypertensive rats (SHRsp), the plasma levels of endothelin were increased, which could be reversed by the treatment with Ipt at the doses of 0.25, 1.0 and 4.0 mg·kg -1 po, once a day, for 3 months. Circled digit two In cultured neonatal bovine aortic endothelial cells (BAEC), Ipt at the concentrations of 1-1000 μmol ·L-1, inhibited the secretion of ET in a concentration-dependent manner. Circled digit three Under the same experimental conditions, Ipt also inhibited the expressions of ET and ECE in BAEC. Circled digit four In isolated preparations derived from rat aorta, the vascular contraction evoked by ET-1 was antagonized by Ipt at the concentrations of 0.5-100 μmol·L-1 in a concentration-dependent manner. The vasorelaxative effects of Ipt were attenuated significantly in buffer without Ca2+. Circled digit five In anaesthetized SD rats, intrapulmonary artery administration of ET-1 induced vascular contraction in vivo, resulting in intrapulmonary artery hypertension, which was prevented by iptakalim hydrochloride at the doses of 0.5-1.0 mg·kg-1. But it had no effects on normal pulmonary artery pressure. Conclusion: Ipt could antagonize the functions of endothelin system. Its characteristics include inhibiting the expression of ET-1 and ECE, inhibiting the releasing of ET-1, reversing the increased plasma levels of ET-1 under pathological condition, and preventing intrapulmonary artery hypertension induced by ET-1.
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Aim To investigate the regulatory effects of Iptakalim hydrochloride(Ipt) on excess expression of monocyte chemoattractant protein-1(MCP-1), intercellular cell adhesive molecule type-1(ICAM-1),vascular cell adhesive molecule1-1(VCAM-1) mRNA in bovine aortic endothelial cells cultured with high concentration D-glucose.Methods The endothelial cells were divided into three groups: control,model and Ipt group.The MCP-1,ICAM-1 and VCAM-1 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR).Results Compared with control group,MCP-1,ICAM-1 and VCAM-1 mRNA expres sion of model group all increased after treatments with 25 mmol?L~(-1) D-glucose for 16 h,respectively.Compare with model group,the excess expression of MCP-1,ICAM-1 mRNA was blocked by 1～10 ?mol?L~(-1) Ipt added for 20 h in advance,respectively but no significant effect was found in the expression of VCAM-1 mRNA.Conclusion High concentration of D-glucose induced excess expression of MCP-1,ICAM-1 and VCAM-1 mRNA,respectively.The excess expression of MCP-1,ICAM-1mRNA is inhibited by Ipt.
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AIM: To investigate the effects of iptakalim hydrohloride on K_(ATP) mRNA expression in renal tissues of spontaneously hypertensive rats. METHODS: SHRs at the age of 12-week-old were treated with Ipt 1, 3, and 9 (mg?kg~(-1)?d~(-1)), benazepril 3 (mg?kg~(-1)?d~(-1)) once a day for 12 weeks, respectively. The same aged WKY rats were used as normal control. The effects of Ipt on BP and renal K_(ATP) mRNA expression were detected by RT-PCR. RESULTS: mRNA expression level of SUR2?Kir6.1 and Kir1.1 increased in SHR. After administration of 1, 3, and 9 (mg?kg~(-1)?d~(-1)) Ipt,the levels of BP were decreased,and the mRNA expression of Kir6.1 and Kir1.1 were decreased. But there was no change in mRNA expression of SUR2. In addition, there was no significantly difference of mRNA expression of Kir6.2 among the SHR groups and the WKY group. CONCLUSION: The renal protective effects of Ipt may be related to regulation of genes expression of Kir6.1 and Kir1.1.
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AIM: To investigate the protective effects and mechanisms of iptakalim hydrochloride(Ipt)on H_2O_2 induced neurotoxity. METHODS: Neurotoxity injury was induced by H_2O_2 in PC12 cells. The cell viability was tested by MTT assay. The glutamate released from PC12 cells was measured by HPLC combined with fluorescent detector analysis. Changes in the intracellular free Ca 2+ concentration ([Ca 2+ ]_i) were determined in fluo-3 AM loaded PC12 cells. RESULTS: Ipt (1, 10 and 100 ?mol?L -1 ) markedly mitigated H_2O_2-induced neurotoxity, 10 ?mol?L -1 Ipt inhibited the release of glutamate and the increase of [Ca 2+ ]_i induced by H_2O_2 .The protective effects was incompletely blocked by 5-HD which is a mitochondrial K_ ATP channels antagnist. CONCLUSION: Ipt provides neuroprotective effects on H_2O_2 induced cytoxixity in cultured PC12 cells and the protective effects may be partially related with mitochondrial KATP channels.
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AIM : To investigate the effects of the new K ATP channel opener, iptakalim (Ipt), on the Parkinsonian symptoms induced by haloperidol in rats. METHODS : Using L -DOPA as the positive drug, the influences of Ipt on latency time, walking time, rearing and grooming of the parkinsonian-like rats induced by haloperidol were observed. RESULTS : Ipt ameliorated hypolocomotion and assuaged catalepsy induced by haloperidol in rats. Moreover, the effects of Ipt ( 0.5 mg?kg -1) were better than those of L -DOPA (100 mg?kg -1). CONCLUSION : Opening of K ATP channels may play a key role in improving Parkinsonian symptoms induced by haloperidol in rats.
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AIM To study the relationship between the activity of glutamate transporters and Parkinson's disease (PD), examine whether a novel ATP sensitive potassium (K ATP) channel opener Iptakalim (Ipt) hydrochloride enhances glutamate uptake activity, and to investigate its mechanisms. METHODS Rats were stereotaxically injected with 6 hydroxydopamine (6 OHDA) in SNpc. The synaptosomes from normal and PD rats were isolated, and [ 3H] glutamate uptake in synaptosomes was measured by using liquid scintillation counting. RESULTS [ 3H] glutamate uptake by synaptosomes from striatum and cerebral cortex of PD rats decreased and the redution was recovered by administration with Ipt (10, 50, 100 ?mol?L -1 ). The protective effect of Ipt was blocked by co adiministration with glibenclamide (20 ?mol?L -1 ), an inhibitor of sulphonylurea receptors. CONCLUSION Our results demonstrate for the first time the protective role of K ATP channel in glutamate uptake of synaptosomes and conceptually support the view that Ipt may have potential and feasibility in therapy for PD.
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AIM To study the experimental therapeutic effects of iptakalim hydrochloride(Ipt) on hypertensive cardiac remodeling in spontaneously hypertensive rats(SHR) and stroke prone spontaneously hypertensive rats(SHRsp). METHODS SHR at the age of 12 week old were treated ig with lisinopril 12 mg?kg -1 ?d -1 or Ipt 3 mg?kg -1 ?d -1 , once a day for 30 days. Age matched Wistar rats were used as normal control. 10 week old SHRsp were treated ig with Ipt 0 25,1 0 and 4 0 mg?kg -1 , once a day for 12 weeks. Age matched Wistar rats were used as normal control. After killing animals, the effects of Ipt on hypertensive cardiac remodeling were investigated. RESULTS During the 4 week experimental period, the systolic blood pressure(SBP) and heart rates(HR) of the untreated SHR were increased progressively. Ipt 3 mg?kg -1 ?d -1 could decrease SBP effectively and inhibit the increasing tendency of HR. Ipt had no effects on hypertensive cardiac remodeling in SHR. Under the same experimental conditions, lisinopril 12 mg?kg -1 ?d -1 could decrease SBP effe-ctively and had no effects on HR. The hypertensive cardiac remodeling could be alleviated by lisinopril. During the 12 week experimental period, the SBP of the untreated SHRsp were increased progressively. Ipt 0 25,1 0 and 4 0 mg?kg -1 could decrease the SBP of SHRsp effectively. Ipt at the doses of 0 25 and 1 0 mg?kg -1 had no effects on heart rates. But in the 4th week after administration of Ipt 4 0 mg?kg -1 , significant decrease in heart rates was observed. Compared with Wistar rats, the weight of left ventricle and septum(LV+S) and the ratio of LV+S to body weight(LV+S/BW) in untreated SHRsp were elevated significantly. Ipt 0 25, 1 0 and 4 0 mg?kg -1 ?d -1 could decrease LV+S and LV+S/BW significantly. CONCLUSION Ipt could decrease SBP of SHR and SHRsp effectively. The effects of Ipt on hypertensive cardiac remodeling were related with the experimental therapeutic period. After having been treated with Ipt for 4 weeks, the hypertensive cardiac remodeling could not be reversed. But after having been treated with Ipt for 12 weeks, the hypertensive cardiac remodeling could be reversed significantly.
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Aim To observe changes of gene expression profile in rat heart , liver and brain treated with iptakalim using cDNA microarray and analyze its molecule mechanism about pharmacology and treatment. Methods ①Rats were treated with iptakalim for 14 days at a dose of 3 mg?kg-1 by gavage. Total RNA was extracted from heart, liver and brain tissues and reversely transcribed to cDNA, which were labeled with Cy3 and Cy5 fluorescent as probes and hybridized to Gene Chip (BiostarR-40s). Scan array 3 000 was used for scanning the hybridizing signals and ImageGENE 3.0 for data analysis. Data were confirmed using RT-PCR. ②Rats were randomly divided into normal control group and 4 iptakalim groups. Iptakalim was administered orally at doses of 1, 3, 9 mg?kg-1 body weight per day for 2 weeks. The last group was orally administered at a dose of 9 mg?kg-1 body weight per day for 2 weeks, and iptakalim was withdrawn for 10 days. We observe effects of iptakalim on hemodynamics parameters in anesthetized rats and changes of myocardial structure, myofilament ultra-structure after 24h at the end of the last administration. Results ① The new chemical entity iptakalim had selectivity on changes of gene expression in rat heart, liver and brain. Compared with control group, 236 genes are changed (100 increased and 136 decreased) in rat hearts and 6 transcripts (6 increased) in rat livers, there are no changes on gene expression in rat brains. ② In anesthetized rats, iptakalim at doses of 1, 3, 9 mg?kg-1 neither affected pharmacological effects on cardiovascular hemodynamics parameters nor had pathological changes on myocardial morphological and ultrastructure. Conclusion Under the same experimental conditions, the new chemical entity iptakalim has selectivity on changes of gene expression in vital organs. Iptakalim shows no side-effects on cardiac function and tissue structure.
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AIM To investigate the effects of iptakalim hydrochloride(Ipt) on potassium currents in cardiomyocytes derived from guinea pig and on the specific binding of glibenclamide (Gli) with sulfonylurea receptor(SUR_ 2A ) of ATP-sensitive potassium channel (K_ ATP ) in cardiac membranes derived from Wistar rats. The effects of Ipt on the association and dissociation kinetic processes of Gli binding with SUR_ 2A of K_ ATP in cardiac preparations were also determined. METHODS The effects of Ipt on potassium currents in cardiomyocytes were observed by using patch clamp technique(whole cell recording) after application of the drug in the bath. The experiments of the ass ociation and dissociation kinetic processes of K_ ATP blocker [ 3H]Gli binding with cardiac membranes were used. RESULTS (1)The potassium current-voltage curves (I-U curves) of cardiomyocytes derived from guinea pig were upward shifted by Ipt at the concentrations of 1 and 100 ?mol?L -1 . Within 5 minutes after application of the drug, the current amplitude increased to 124.9%?9.5%(n=5)and 151.6%?11.2%(n=7)of initial current amplitude respectively(P
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AIM To investigate the effects of iptakalim hydrochloride(Ipt) on the association and dissociation kinetic processes of [ 3H]glibenclamide(Gli) binding with sulfonylurea receptor(SUR 2B ) of ATP sensitive potassium channel (K ATP ) in vascular smooth muscles derived from Wistar rats,and to compare the properties of Ipt with those of nucleotides. The interactions between Ipt and nucleotides were also determined. METHODS The experiments of the association and dissociation kinetic processes of K ATP blocker[ 3H]Gli binding with endothelium denuded aorta smooth muscles were used. RESRLTS (1)The specific bindings of[ 3H]Gli with SUR 2B were not displaced by Ipt at the concentrations of 10 pmol?L -1 ～ 0 5 mmol?L 1 . Ipt 100 ?mol?L -1 retarded the association kinetic process and accelerated the dissociation kinetic process of [ 3H]Gli binding with SUR 2B . (2)Opposite to Ipt, ATP 1 mmol?L -1 accelerated the association kinetic process and retarded the dissociation kinetic process of [ 3H]Gli binding with SUR 2B There was an interaction between ATP and Ipt in the modulation of [ 3H]Gli binding with SUR 2B . (3) Similar with Ipt, ADP 1 mmol?L -1 retarded the association kinetic process and accelerated the dissociation kinetic process of [ 3H]Gli binding with SUR 2B , there was an interaction between ADP and Ipt in the modulation of [ 3H]Gli binding with SUR 2B . (4)Different from ATP and ADP, UDP had no effect on the association and dissociation kinetic process of [ 3H]Gli binding with SUR 2B . And there was not interaction between UDP and Ipt. CONCLUSION Ipt had no affinity with the binding sites of K ATP blocker in SUR 2B , but had negative allosterical modulation on it. The modulatory properties of Ipt were opposite to those of ATP, similar with those of ADP and different from those of UDP. There were interactions between ATP, ADP and Ipt in the modulation of [ 3H]Gli binding with SUR 2B , but there was not interaction between UDP and Ipt.
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Aim To investigate the effect of iptakalim on neonatal cardiomyocytes hypertrophy induced by isoprenaline(ISO).Methods Hypertrophy in neonatal rat cardiac myocytes was established via culture with ISO.Total protein content was measured by Lowrys method.The fluorescence intensity of intracellular Ca2+ was detected respectively with Fluo-3/AM loading by the laser confocal microscopy.Results ① 1?10-5mol?L-1 ISO can activated ?-AR completely;② the total protein of cardiomyocytes and intracellular i was markedly decreased by treatment with IPT and represented a dose-dependent manner.Conclusion IPT could inhibit the increase of protein content of cardiomyocytes induced by ISO,which may be contributed to the decease of intracellular Ca2+ concentration.
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Aim To investigate the therapeutic effects of Iptakalim hydrochloride on brain damage and blood rheological changes induced by focal cerebral ischemia. Methods The rat model of focal cerebral ischemia was induced by middle cerebral artery occlusion using a suture method. Infarct size was evaluated by TTC staining. Neurological deficit score was evaluated by Longas method. Cerebral water content of the ischemic hemisphere was measured using wet-and-dry-weight method. The erythrocyte membrane fluidity was studied by the fluorescence polarization technique with DPH fluorescence probe. Results Infarct size of the brain was (24.75?6.66)% of contralateral hemisphere 6 h after focal cerebral ischemia.Pretreatment of Ipt 1.0～4.0 mg?kg -1,given inperitoneal,decreased the infarct size by 0.95%,6.6%(P
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AIM To investigate the effects of iptakalim hydrochloride (Ipt) on cerebral neuronal sodium, calcium and potassium channels. METHODS The effects of Ipt on sodium, calcium and potassium channels in cultured hippocampal neurons was observed using whole-cell recording technique. RESULTS Ipt had no significant effect on Na +, Ca 2+ currents, but significantly increased the outward K + currents. This enhancement of Ipt was inhibited by synchronously application of glibenclamide. Upon the administration of Ipt 1, 10, 100 ?mol?L -1, the outward K + current was significantly increased to (121.9?8.1)%, (114.7?7.1)%, (109.1?10.0)% respectively (n=6～9, P
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AIM To investigate the protective effects of iptakalim hydrochloride (Ipt) against glutamate induced neurotoxity. METHODS Neurotoxity injury was induced by with glutamic acid in PC12 cells. The cell viability was measured by MTT assay. RESULTS Ipt at the concentrations of 1 ? 1(T-10 - 1 ? 1(T4 mol ? L-1 markedly mitigated glutamate-induced neurotoxicity. The protec- live effect was nullified by glibenclamide, an ATP-sensitive potassium channel antagnist. CONCLUSION Ipt provides neuroprotection on glutamate-induced cytotoxixity in cultured PC12 cells and this effect may be related with ATP-sensitive potassium channels.
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AIM To investigate the effects of the novel antihypertensive drug iptakalim hydrochloride on potassium currents in artery smooth muscle cells. METHODS The effects of iptakalim hydrochloride on potassium currents in smooth muscle cells derived from rat pulmonary arteries were observed by using patch clamp technique(whole cell recording) after application of the drug in the bath. RESULTS The potassium current-voltage curves ( I-U curves) of smooth muscle cells derived from normotensive rat pulmonary arteries were up-ward shifted by iptakalim hydrochloride(0.1,1,10 and 100 ?mol?L -1 ). Within 5 minutes after application of the drug, the current amplitude could increase to[(118.6?15.9)%, P