iptakalim

OBJECTIVE: To study the selective dilatation effects of iptakalim (Ipt), a novel ATP-sensitive potassium channel opener, on pulmonary arterioles in hypoxic pulmonary hypertensive rat. METHODS: SD male rats were divided into 3 groups, control group, the rest were fed in hypoxic and normobaric environment (O2 10% +/- 0.5%, 8 h/d and 6 d/week) and divided into hypoxia group and hypoxia plus acetazolamide (Acz) group (hypoxic rats were treated with ig acetazolamide (Acz) 80 mg x kg(-1) d(-1)) ...

OBJECTIVE: To study the effects of iptakalim (Ipt), an ATP-sensitive potassium channel opener, on cardiac remodeling induced by isoproterenol (ISO) in Wistar rats. METHODS: ISO was given subcutaneously (85 mg/(kg x d), sc, 7 days) to induce cardiac remodeling in rats. The rats in Ipt treated group were administrated with Ipt 3 mg/kg (po) after ISO injection. After treated with Ipt for 6 weeks, the hemodynamic parameters were tested by an eight channel physiological recorder (RM-6000)...

Iptakalim is an ATP-sensitive potassium channel opener, as well as an α4β2-containing nicotinic acetylcholine receptor (nAChR) antagonist. Pretreatment with iptakalim diminishes nicotine-induced dopamine (DA) and glutamate release in the nucleus accumbens. This neuropharmacological profile suggests that iptakalim may be useful for treatment of nicotine dependence. Thus, we examined the effects of iptakalim in two preclinical models. First, the impact of iptakalim on the interoceptive stimulus effect of nicotine was evaluated by training rats in a discriminated goal-tracking task that included intermixed nicotine (0...

BACKGROUND: ATP-sensitive potassium (K-ATP) channels couple cellular metabolism to electric activity. Although Kir6.2-composed K-ATP channel (Kir6.2/K-ATP channel) has been demonstrated to regulate inflammation, a common cause of most liver diseases, its role in liver injury remains elusive. METHODS: Kir6.2 knockout mice were used to prepared LPS-induced liver injury model so as to investigate the role of Kir6.2/K-ATP channels in the injury. Histochemistry was applied to evaluate the extent of liver injury...

Cumulative evidence suggests that renal vascular endothelial injury play an important role in initiating and extending tubular epithelial injury and contribute to the development of ischemic acute renal failure. Our previous studies have demonstrated that iptakalim's endothelium protection is related to activation of SUR2B/Kir6.1 subtype of ATP sensitive potassium channel (K(ATP)) in the endothelium. It has been reported that SUR2B/Kir6.1 channels are widely distributed in the tubular epithelium, glomerular mesangium, and the endothelium and the smooth muscle of blood vessels...

Hypoxic pulmonary hypertension (HPH) is a syndrome characterized by the increase of pulmonary vascular tone and the structural remodeling of peripheral pulmonary arteries. The aim of specific therapies for hypoxic pulmonary hypertension is to reduce pulmonary vascular resistance, reverse pulmonary vascular remodeling, and thereby improving right ventricular function. Iptakalim, a lipophilic para-amino compound with a low molecular weight, has been demonstrated to be a new selective ATP-sensitive potassium (K(ATP)) channel opener via pharmacological, electrophysiological, biochemical studies, and receptor binding tests...

Iptakalim is a new ATP-sensitive potassium (KATP) channel opener, and it inhibits the proliferation of pulmonary arterial smooth muscle cells (PASMCs) and pulmonary vascular remodeling. However, the underlying mechanism remains unclear. In the present study, we found that iptakalim significantly decreased pulmonary artery pressure, inhibited pulmonary ariery remodeling and PKC-α overexpression in chronic hypoxia in a rat pulmonary hypertension model. Iptakalim reduced hypoxia-induced expression of PKC-α, and abolished the effect of hypoxia on PASMC proliferation significantly in a dose-dependent manner in vitro...

OBJECTIVE: Iptakalim is a putative ATP-sensitive potassium (K(ATP)) 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...

Iptakalim is a novel K(ATP) opener with antihypertensive properties. The Kir6.1 gene is one of the candidate genes that may influence the response to iptakalim in hypertensive patients. We aimed to ascertain whether a mutation in the coding region of the Kir6.1 gene is present in Chinese Han hypertensive patients. The study population included 162 Chinese Han hypertensive patients (81 men and 81 women with a mean age of 55±9 years). Mutational analysis of the coding region of Kir6.1 was performed using PCR-SSCP and direct sequencing...

The aim of this study was to assess whether hypoxia inhibits endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production, and whether iptakalim may rescue human pulmonary artery endothelial cells (HPAECs) from hypoxia-induced NO system dysfunction. HPAECs were cultured under hypoxic conditions in the absence or presence of 0.1, 10 and 1,000 μM iptakalim or the combination of 10 μM iptakalim and 1, 10 and 100 μM glibenclamide for 24 h, and the eNOS activity and NO levels were measured in the conditioned medium from the HPAEC cultures...

OBJECTIVES: We sought to investigate the experimental therapeutic effects and mechanisms of iptakalim, a new adenosine triphosphate (ATP)-sensitive potassium channel (K(ATP)) opener, on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and right heart ventricle remodeling in rats. METHODS: Rats were injected with a single dose (50 mg/kg, ip) of MCT and given iptakalim (1, 3, and 9 mg/kg·per d, orally [po]) or saline for 28 days. The hemodynamic and morphometric parameters were assessed...

BACKGROUND AND PURPOSE: Emerging evidence indicates that stimulating adult neurogenesis provides novel strategies for central nervous system diseases. Iptakalim (Ipt), a novel ATP-sensitive potassium (K-ATP) channel opener, has been demonstrated to play multipotential neuroprotective effects in vivo and in vitro. However, it remains unknown whether Ipt could regulate the adult neurogenesis. METHODS AND RESULTS: Based on the finding that adult neural stem cells (ANSCs) in hippocampus expressed Kir6...

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OBJECTIVES: To investigate the safety, pharmacokinetics and food effect of iptakalim in healthy adult Han Chinese volunteers. METHODS: Study 1 was a randomized open-label, Latin square designed, single-dose, three-period, self-control crossover study. Six men and six women received 5, 10 and 20 mg of iptakalim orally. Study 2 was a randomized, open-label, single-dose, two-period, self-control crossover study. Ten men were included and each subject received 5 mg iptakalim orally, fasting and nonfasting...

OBJECTIVE: To study the effects of iptakalim (IPT) on pressure-overload induced cardiac remodeling in rats, and investigate correlation between this protection effects and plasma PGI2 content. METHOD: The pressure-overload induced cardiac remodeling model was induced by abdominal aorta constriction for 6 weeks, and the rats were divided into 5 groups repectively: (1) sham group, (2) control group, (3) IPT 3 mg/kg group (IPT 3), (4) indomethacin 2 mg/kg group (Indo 2), (5) indomethacin 2 mg/kg + IPT 3 mg/kg group (Indo 2 + IPT 3)...

AIM: To investigate the effects of iptakalim on endothelial dysfunction induced by insulin resistance (IR) and to determine whether iptakalim improved IR associated with hypertension in fructose-fed rats (FFRs) and spontaneously hypertensive rats (SHRs). METHODS: Human umbilical vein endothelial cells (HUVECs) were used for in vitro study. The levels of endothelial vasoactive mediators and eNOS protein expression were determined using radioimmunoassays, ELISAs, colorimetric assays or Western blotting...

OBJECTIVE: To investigate the role of iptakalim, an ATP-sensitive potassium channel opener, in transient cerebral ischemia/reperfusion (I/R) injury and its involved mechanisms. METHODS: Intraluminal occlusion of middle cerebral artery (MCAO) in a rat model was used to investigate the effect of iptakalim at different time points. Infarct volume was measured by staining with 2,3,5-triphenyltetrazolium chloride, and immunohistochemistry was used to evaluate the expressions of Bcl-2 and Bax...

AIM: To study the relationship between the antihypertensive response of iptakalim and KCNJ11 polymorphisms in Chinese Han hypertensive patients. METHODS: One hundred sixty two Chinese Han hypertensive patients were administered iptakalim (5 or 10 mg/d, po) for 8 weeks. Before the treatment and 24 h after completing the treatment blood pressure (BP) was measured. Genotyping was performed using direct sequencing. RESULTS: Four common A190A, E23K, I337V and 3'UTR +62 G/A polymorphisms were found in KCNJ11...

AIM: To elucidate the modulation of the chemerin/ChemR23 axis by iptakalim-induced opening of K(ATP) channels and to determine the role of the chemerin/ChemR23 axis in the iptakalim-mediated endothelial protection. METHODS: Cultured rat aortic endothelial cells (RAECs) were used. Chemerin secretion and ChemR23 protein expression were investigated using Western blot analysis. The gene expression level of ChemR23 was examined with RT-PCR. In addition, the release of nitric oxide (NO) was measured with a nitric oxide assay...

AIM: To investigate the differences of membrane capacitance, membrane current, current density and I-V curves between smooth muscle cells isolated from RHR and NTR pulmonary arteries. METHODS: Under antiseptic conditions, the left renal artery was exposed through a retroperitoneal flank incision and carefully dissected free of the left renal vein. A silver clip with an internal diameter of 0.2-0.3 mm was placed around the left renal artery, resulting in partial occlusion of renal perfusion...