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国际生理学与病理学期刊
SJR: 0.116

ISSN 打印: 2155-014X
ISSN 在线: 2155-0158

Archives: Volume 1, 2010 to Volume 9, 2018

国际生理学与病理学期刊

DOI: 10.1615/IntJPhysPathophys.v8.i2.30
pages 121-130

The Role of TRPV4 Cation Channels in Regulation of Phenylephrine-Induced Contraction of Rat Pulmonary Artery

Dariia Dryn
Taras Shevchenko National University of Kyiv, Institute of Biology and Medicine, Kyiv, Ukraine; Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
Mariia Melnyk
Institute of Pharmacology and Toxicology, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
Ihor Kizub
Institute of Pharmacology and Toxicology, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
Hongzhen Hu
Washington University School of Medicine, St. Louis, USA
Anatoly I. Soloviev
Institute of Pharmacology and Toxicology, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
Alexander Zholos
Taras Shevchenko National University of Kyiv, Institute of Biology and Medicine, Kyiv, Ukraine; Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine

ABSTRACT

The aim of the study was to investigate the role of vanilloid transient receptor potential cation channel (TRPV4) in the regulation of rat pulmonary artery smooth muscle (PASM) contractile activity induced by the activation of α1-adrenoceptors and study them as a potential target for pharmacological intervention in pulmonary hypertension. TRPV4 selective agonist, GSK1016790A, in the presence of the α1-adrenoceptor agonist phenylephrine (PhE) evoked biphasic contractile reaction with initial relaxation (63.5% ± 7.1) followed by a significant vasoconstriction (142% ± 17.9%). GSK1016790A evoked similar effects on the PASM rings with endothelium and without it, indicating that its main site of action was TRPV4 expressed in smooth muscle cells. TRPV4 selective blocker, HC-067047, completely inhibited the effects of GSK1016790A confirming the specific role of TRPV4 in those vascular responses. Application of Ca2+-free external solution reduced the relaxation phase and completely abolished the sustained contractile response to GSK1016790A (from 43.9% to 0.3%). The biphasic dilation-constriction response could be explained by an initial calcium store depletion by PhE and further calcium-induced calcium release from the sarcoplasmic reticulum through TRPV4 channels to cause BKCa activation, membrane hyperpolarisation and vasorelaxation. Further Ca2+ entry via TRPV4 channels causes contraction. We have concluded that TRPV4 channels play an important role in the regulation of the pulmonary artery vascular tone, but TRPV4 activation mechanism(s) and signaling pathways remain unclear.


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