Effects of Iptkalim hydrochloride on mRNA level of ATP-sensitive potassium channels of pulmonary artery smooth muscles in chronic hypoxic rats

Abstract

Abstract: AIM: To study mRNA expression of ATP-sensitive potassium channels (K_ATP) of pulmonary artery in chronic hypoxic pulmonary artery hypertension (CHPAH) rats and in chronic hypoxic rats treated with novel K_ATP opener Iptkalim hydrochloride.METHODS: Sixteen Sprague-Dawley(SD) male rats were randomly divided into control group, hypoxic group, low dose Iptkalim group (0.75 mg·kg^-1·d^-1), and high dose Ipkalim group (1.5 mg·kg^-1 ·d^-1).Except the first group, the other three groups were put into hypoxic and normobaric chamber to establish chronic hypoxic model.Four weeks later, reverse transcription polymerase chain reaction (RT-PCR) was performed to analyze the mRNA level of K_ATP channels in pulmonary main artery smooth muscles. RESULTS: The mRNA levels of SUR2 in the hypoxic group were significantly lower than those in the control group, this decrease was completely reversed by Iptkalim in high dose group, and no difference in Kir 6.1 mRNA level was found between four groups.CONCLUSION: K_ATP channel transcriptional expression is inhibited by chronic hypoxia, and this inhibition can be up-regulated by Iptkalim.The role of potassium channel in the development of CHPAH may explain the therapeutic mechanism of Iptkalim.

Key words: ATP-sensitive potassium channel, chronic hypoxic pulmonary artery hypertension, Iptkalim hydrochloride, pulmonary artery smooth muscle, mRNA, RT-PCR

CLC Number:

R965.1

SHEN Hong, WANG Hong, XIE Wei-Ping, HU Gang. Effects of Iptkalim hydrochloride on mRNA level of ATP-sensitive potassium channels of pulmonary artery smooth muscles in chronic hypoxic rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(4): 389-393.

References

1 Brayden JE.Functional roles of K_ATP channels in vascular smooth muscles[J].Clin Exp Pharmacol Physiol, 2002;29 (4):312-6
2 Wang J, Juhaszova M, Rubin LJ, Yuan XJ.Hypoxia inhibits gene expression of voltage-gated K⁺ channel αsubunits in pulmonary artery smooth muscle cells[J].J Clin Invest, 1997;100 (9):2347-53
3 Cui Y, Tran S, Tinker A, Clapp LH.The molecular composition of K_ATP channels in human pulmonary artery smooth muscle cells and their modulation by growth[J].Am J Respir CellMol Biol, 2002;26(1):135-43
4 Cao K, Tang GH, Hu DH, Wang R.Molecular basis of ATPsensitive channels in rat vascular smooth muscles[J].Biochem Biophys Res Commun, 2002;296(2):463-9
5 Ranki HJ, Budas GR, Crawford RM, Jovanovic A.Genderspecific difference in cardiac ATP-sensitive K⁺ channels[J]. JACC, 2001;38(3):905-15
6 Horinaka S, Kobayashi N, Higashi T, Hara K, Hara S, Matsuoka H.Nicorandil enhances cardiac endothelial nitric oxide synthase expression via activation of triphosphate-sensitive K channel in rat[J].J Cardiovasc Pharmacol, 2001;38(2):200-10
7 Mandegar M, Yuan JXJ.Role of K⁺ channels in pulmonary hypertension[J].Vascular Pharmocol, 2002;38(1):25-33
8 Sato K, Morio Y, Morris KG, Rodman DM, McMurtry IF. Mechanism of hypoxic pulmonary vasoconstriction involves ETA receptor-mediated inhibition of K_ATP channels[J].Am J Physiol, 2000;278(3):L434-42
9 Peng W,Michael JR, Hoidal JR.ET-1 modulates Kca-channels activity and arterial tension in normoxic and hypoxic human pulmonary vasculature[J].Am J Physiol, 1998;275(4):L729-39
10 Platoshyn O, Golovina VA, Bailey C, Limsuwan A, Krick S, Juhaszova M, et al.Sustained membrane depolarization and pulmonary artery smooth muscles cell proliferation[J].Am J Phy siol, 2000;279(5):C1540-9
11 Cells SM, Channels I.The pathobiology of pulmonary hypertension[A].In:Rich S, McLaughlin VV, eds.Pulmonary Hypertension[M].Philadelphia:W.B.Saunders Company, 2001:419-32
12 Nakayama K, Fukuta Y, Kiyoshi A, Iwatsuki Y, Ishii K, Ishikawa T, et al.(+)-[³H] Isradipine and [³H] Glyburide bindings to heart and lung membranes from rats with monocrotaline-induced pulmonary hypertendion[J].Jpn J Pharmacol, 1999;81(2):176-84
13 Muramatsu M, Oka M, Morio Y, Soma S, Takahashi H, Fukuchi Y.Chronic hypoxia augments endothelin-B receptormediated vasodilation in isolated perfused rat lungs[J].Am J Physiol, 1999;276(2):L358-64

[1]	LIU Chun, WANG Meng, CHENG Hui, LI Qinglin. Mechanism of gambogenic acid inhibiting the proliferation of melanoma based on RNA-seq sequencing technology [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(2): 155-163.
[2]	SHEN Chang, AI Kelong, HU Changping. Research progress in the regulation of hypoxic pulmonary hypertension by hypoxia-inducible factor-1 signaling pathway [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(1): 114-120.
[3]	CHENG Yuan-guang, WU Pei. Expression of somatostatin receptor type 2 in colorectal cancer [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(10): 1100-1104.
[4]	WANG Yong-hui, QI Jin-feng, LIN Mei. Effect of total saikosaponins on the intestinal first-pass effect and liver Cyp3a, Cyp2e1 [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(7): 740-748.
[5]	SHI Liang-hui, ZHANG Cai-quan, PENG Xiao-zhuang. Relationship between the expression of LAT1,CD98hc and clinical pathological characteristics of gastric carcinoma [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(12): 1361-1366.
[6]	ZHANG Hao-chuan,CHEN Cong-de,BAO Xiao-zhou,CHEN Xiao-ming. Effects of di (2-ethylhexyl) phthalate on the prostaglandin E-2 levels and cyclooxygenase-2 mRNA expression of testicular tissue in adult rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(1): 38-41.
[7]	HUANG Lai-quan, WEI Zhong-lin, ZHANG Jun, ZHANG Dai-yun, WANG Xing-hong. Expressions of BAG-1 and NF-κB P65 in the mononuclearcell of multiplemyeloma patients [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(3): 292-297.
[8]	SHUAI Xun-jun, GONG Qian-hong, AI Deng-bin, FU Shi-ou. Effects of edaravone on interleukin-6,-8 and expression of their mRNA in patients undergoing one lung ventilation [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(3): 326-330.
[9]	CUI Wen-yu, NIE Hong-jing, ZHANG Dong-xiang, XIAO Zhong-hai, ZHANG Yan-fang, CUI Jian-hua, SHI Yong-ping, LONG Chao-liang, WANG Yin-hu, WANG Hai. Effects of ATP-sensitive potassium channel opner iptakalim on deacclimatization to high altitude [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(2): 190-193.
[10]	ZENG Hui, LIU Zhao-qian. Effect of histamine on fat synthesis and regulation in the white adipocytes: a mechanism research [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(12): 1343-1347.
[11]	LI Meng-qiu, DOU Jie, DU Wei, LI Xin-ya, LIN Jian, ZHOU Chang-lin. Effects of tripterine on the immunosuppression action and expression of IL-6 mRNA in mice [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(2): 158-163.
[12]	LI Qiang-xiang, WANG Cai-yun, OU Yu-lan, HE Jin-lian, ZHU Fei-yue, ZHANG Zhuo, ZHONG Hui-ju. Effects of puerarin on blood lipid and expression of aorta laminin B1 mRNA in streptozotocin-induced diabetic rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(8): 883-887.
[13]	DAI Cui-ping, ZENG Xiao-ning, SUN Xiu-lan, DING Jian-hua, HU Gang. Diazoxide increases glutamate uptake by astrocytes via activating mitochondrial ATP-sensitive potassium channels [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(4): 398-401.
[14]	LI Yun-man, KANG Kai, FANG Wei-rong. Lomerizine inhibits activity of P-glycoprotein in primary cultured brain microvessel endothelial cell monolayers [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(10): 1110-1114.
[15]	YU Hong-e, YU Qing-sheng, LIU Xin-yan, ZHU Liu, LOU Xiao-hua, TENG Mai-kun. China cobra venom active factor (CCVAF) inhibits VEGF and bFGF in lung cancer cell line H1299 [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(9): 970-973.