Impact of nitrate therapy on the expression of caveolin-1 and its phosphorylated isoform in lungs in the model of monocrotaline induced pulmonary hypertension

European Pharmaceutical Journal Pub Date : 2018-11-01 DOI:10.2478/afpuc-2018-0002

Z. Kmecová, E. Malikova, B. Zsigmondova, M. Radik, J. Vetešková, M. Marušáková, P. Krenek, J. Klimas

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Abstract

Abstract Aim: Nitric oxide signalling pathway showed to be one of the crucial factors in the treatment and pathogenesis of pulmonary arterial hypertension. The aim of this study was to determine the effect of administration of inorganic nitrate, NaNO3, on the expression of caveolin-1 and its phosphorylated isoform (pTyr14Cav-1) in lungs in the experimental model of monocrotaline induced pulmonary hypertension. Methods: 10 weeks old male Wistar rats were subcutaneously injected with 60 mg/kg dose of monocrotaline (MCT) or vehicle (CON). Twelve days after the injection, part of the MCT group was receiving 0.3 mM NaNO3 (MCT+N0.3) daily in the drinking water and rest was receiving 0.08% NaCl solution. Four weeks after MCT administration, the rats were sacrificed in CO2. Protein expression in lungs was determined by western blot. Results: We observed a significant decrease in the caveolin-1 expression and a significant shift towards the expression of pTyr14Cav-1 in the group treated with nitrate (p < 0.05). Conclusion: NaNO3 administration affected the expression of caveolin-1 and the ratio of its active (phosphorylated) isoform increased.

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硝酸盐治疗对单芥碱诱导肺动脉高压模型肺内小窝蛋白-1及其磷酸化异构体表达的影响

摘要目的：一氧化氮信号通路是肺动脉高压治疗和发病机制中的重要因素之一。本研究的目的是确定在野百合碱诱导的肺动脉高压实验模型中，施用无机硝酸盐NaNO3对小窝蛋白-1及其磷酸化异构体（pTyr14Cav-1）在肺中表达的影响。方法：10周龄雄性Wistar大鼠皮下注射野百合碱（MCT）或赋形剂（CON）60mg/kg。注射后12天，部分MCT组每天在饮用水中接受0.3mM NaNO3（MCT+N0.3），其余接受0.08%NaCl溶液。MCT给药四周后，在CO2中处死大鼠。蛋白质在肺中的表达通过蛋白质印迹测定。结果：硝酸盐处理组小窝蛋白-1表达显著下降，pTyr14Cav-1表达显著转移（p<0.05）。

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来源期刊

European Pharmaceutical Journal Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)

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0.60

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期刊介绍： European Pharmaceutical Journal publishes only original articles not previously published and articles that are not being considered or have not been submitted for publication elsewhere. If parts of the results have been published as conference abstract or elsewhere, it should be stated in references. The ethical standards of the Helsinki-Tokio Declaration should be kept. This should be mentioned in the Methods of manuscript. Reviews are published only on request. Authors, whose submitted research work was performed with the support of a company, should indicate this in Conflict of Interest.