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Qi Xu, Xiang Wu, Yu Li, Hui Kong, Yu Jin, Weiping Xie, Hong Wang
OBJECTIVES: Pulmonary vascular medial hypertrophy in hypoxic pulmonary arterial hypertension (HPH) is caused in part by decreased apoptosis in pulmonary artery smooth muscle cells (PASMCs). Iptakalim (Ipt), an ATP sensitive potassium channel opener, ameliorates HPH in animal models. Here we investigated the effects of Ipt on proliferation and apoptosis of hypoxic rat PASMCs, and to determine the possible underlying mechanisms. METHODS: Primary rat PASMCs were isolated and cultured...
October 5, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yan Wu, Meng-Yu He, Jian-Kui Ye, Shu-Ying Ma, Wen Huang, Yong-Yue Wei, Hui Kong, Hong Wang, Xiao-Ning Zeng, Wei-Ping Xie
Accumulating data, including those from our laboratory, have shown that the opening of ATP-sensitive potassium channels (KATP ) plays a protective role in pulmonary vascular diseases (PVD). As maintainers of the endothelial framework, endothelial colony-forming cells (ECFCs) are considered excellent candidates for vascular regeneration in cases of PVD. Although KATP openers (KCOs) have been demonstrated to have beneficial effects on endothelial cells, the impact of KATP on ECFC function remains unclear. Herein, this study investigated whether there is a distribution of KATP in ECFCs and what role KATP play in ECFC modulation...
October 6, 2016: Journal of Cellular and Molecular Medicine
Qinglin Li, Xiaopei Yan, Hui Kong, Weiping Xie, Hong Wang
The aim of the present study was to determine the effect of an ATP-sensitive K+ (KATP) channel opener iptakalim (IPT) on the proliferation and apoptosis of human pulmonary artery smooth muscle cells (HPASMCs), and examine the potential value of IPT to hypoxic pulmonary hyper-tension (HPH) at a cellular level. HPASMCs were divided into the control, ET-1, ET-1+IPT and ET-1+IPT+glibenclamide (GLI) groups. GLI was administered 30 min prior to ET-1 and IPT. The 4 groups were incubated with corresponding reagents for 24 h...
July 2016: Molecular Medicine Reports
Hong-min Zhou, Ming-li Zhong, Ru-huan Wang, Chao-liang Long, Yan-fang Zhang, Wen-yu Cui, Hai Wang
The primary object of this fundamental research was to survey the synergistic cardiovascular effects of iptakalim, a novel ATP-sensitive potassium channel (K(ATP)) opener, and clinical first-line antihypertensive drugs, such as calcium antagonists, thiazide diuretics and β receptor blockers by a 2 x 2 factorial-design experiment. It would provide a theoretical basis for the development of new combined antihypertensive therapy program after iptakalim is applied to the clinic. Amlodipine besylate, hydrochlorothiazide and propranolol were chosen as clinical first-line antihypertensive drugs...
November 2015: Chinese Journal of Applied Physiology
Su-yang Wang, Wen-yu Cui, Hai Wang
AIM: To investigate the mechanisms underlying the activation of ATP-sensitive potassium channels (K(ATP)) by iptakalim in cultured rat mesenteric microvascular endothelial cells (MVECs). METHODS: Whole-cell KATP currents were recorded in MVECs using automated patch clamp devices. Nucleotides (ATP, ADP and UDP) were added to the internal perfusion system, whereas other drugs were added to the cell suspension on NPC-1 borosilicate glass chips. RESULTS: Application of iptakalim (10 and 100 μmol/L) significantly increased the whole-cell K(ATP) currents, which were prevented by the specific K(ATP) blocker glibenclamide (1...
December 2015: Acta Pharmacologica Sinica
Yi Fan, Hui Kong, Xinhai Ye, Jianhua Ding, Gang Hu
ATP-sensitive potassium (K-ATP) channels have been shown to couple membrane electrical activity to energy metabolism in a variety of cells and are important in several physiological systems. In the brain, K-ATP channels are strongly expressed in the neuronal circuitry. The distributional profile and functional significance of K-ATP channels suggest that they may be involved in stress-induced depression. First, we showed that chronic mild stress (CMS) significantly increased the expression of hippocampal Kir6...
July 2016: Brain Structure & Function
Wenrui Liu, Hui Kong, Xiaoning Zeng, Jingjing Wang, Zailiang Wang, Xiaopei Yan, Yanli Wang, Weiping Xie, Hong Wang
Chronic airway diseases are characterized by airway remodeling which is attributed partly to the proliferation and migration of airway smooth muscle cells (ASMCs). ATP-sensitive potassium (KATP) channels have been identified in ASMCs. Mount evidence has suggested that KATP channel openers can reduce airway hyperresponsiveness and alleviate airway remodeling. Opening K(+) channels triggers K(+) efflux, which leading to membrane hyperpolarization, preventing Ca(2+)entry through closing voltage-operated Ca(2+) channels...
August 15, 2015: Experimental Cell Research
Juan Ji, Hui Yan, Zheng-Zhen Chen, Zhan Zhao, Dan-Dan Yang, Xiu-Lan Sun, Yong-Ping Shi
It has been reported that the novel ATP-sensitive potassium (K-ATP) channel opener iptakalim (IPT) decreases ischemic neuronal damage in rats. However, the mechanisms underlying neuroprotection are still to be fully elucidated. The results of this study showed that mice with ischemia induced by middle cerebral artery occlusion exhibited higher mortality and more neurological deficits, as well as larger infarct volume, compared with sham mice. Moreover, it was found that ischemia activated astrocytes surrounding CA1 neurons with an increased expression of D-serine, induced greater microglial activation accompanied by higher tumor necrosis factor alpha (TNF-α) production, and caused higher expressions of matrix metalloproteinase 9 (MMP-9) in the endothelial cells of mice...
July 2015: Clinical and Experimental Pharmacology & Physiology
Rong Zhu, Li-Qing Bi, Su-Ling Wu, Lan Li, Hui Kong, Wei-Ping Xie, Hong Wang, Zi-Li Meng
The present study aimed to investigate the protective effects of iptakalim, an adenosine triphosphate (ATP)-sensitive potassium channel opener, on the inflammation of the pulmonary artery and endothelial cell injury in a hypoxia-induced pulmonary arterial hypertension (PAH) rat model. Ninety-six Sprague-Dawley rats were placed into normobaric hypoxia chambers for four weeks and were treated with iptakalim (1.5 mg/kg/day) or saline for 28 days. The right ventricle systolic pressures (RVSP) were measured and small pulmonary arterial morphological alterations were analyzed with hematoxylin and eosin staining...
August 2015: Molecular Medicine Reports
Jing-Hui Huang, Wen-Zhi Han, Xin Jin, Wei Liu, Hai Wang
OBJECTIVE: To study the selective dilatation effects of iptakalim (Ipt) on basilar and pulmonary arterioles, and endothelial cell function of these arterioles in hypoxic rats. METHODS: SD male rats were divided into 2 groups:control and hypoxic group fed in normobaric hypoxic environment (O2 7.8%, 8 h). Arteriole rings about (204 + 5) pm were isolated and the tension of hypoxic arterioles pre-contracted by 6 nmol/L endothelin-1 (ET-1) was observed with wire myograph system model (DMT 610 m)...
January 2014: Chinese Journal of Applied Physiology
Ming Lu, Jing-Zhe Yang, Fan Geng, Jian-Hua Ding, Gang Hu
Depression is a serious mental disorder in the world, but the underlying mechanisms remain unclear and the effective cures are scarce. Iptakalim (Ipt), an ATP-sensitive potassium (K-ATP) channel opener that can cross the blood-brain barrier freely, has been demonstrated to inhibit neuro-inflammation and enhance adult hippocampal neurogenesis. But it is unknown whether Ipt is beneficial to therapy of depression by modulating neurogenesis and neuro-inflammation. This study aimed to determine the potential antidepressant efficacy of Ipt in a chronic mild stress (CMS) mouse model of depression...
September 2014: International Journal of Neuropsychopharmacology
Jing-Hui Huang, Wen-Zhi Han, Yan-Fang Zhang, Rui-Feng Duan, Hao-Hao Deng, Yu-Hong Guo, Wei Liu, Hai Wang
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)) ...
July 2013: Chinese Journal of Applied Physiology
Ming-Li Zhong, Hui Wang, Hong-Min Zhou, Yan-Fang Zhang, Wen-Yu Cui, Chao-Liang Long, Lian Duan, Hai Wang
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)...
May 2013: Chinese Journal of Applied Physiology
S Charntikov, N Swalve, S Pittenger, K Fink, S Schepers, G C Hadlock, A E Fleckenstein, G Hu, M Li, R A Bevins
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...
December 2013: Neuropharmacology
Ren-Hong Du, Jun Tan, Nan Yan, Ling Wang, Chen Qiao, Jian-Hua Ding, Ming Lu, Gang Hu
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...
April 2014: Journal of Gastroenterology
Ying Zhao, Hai Wang
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...
November 2012: Chinese Journal of Applied Physiology
Yu Jin, Wei-Ping Xie, Hong Wang
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...
November 2012: Chinese Journal of Applied Physiology
Xiangrong Zuo, Feng Zong, Hui Wang, Qiang Wang, Weiping Xie, Hong Wang
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...
November 2011: Journal of Biomedical Research
Nick Volf, Gang Hu, Ming Li
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...
December 2012: Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology
Ruifeng Duan, Wenyu Cui, Hai Wang
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...
July 2011: Experimental and Therapeutic Medicine
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