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200 1 _aAntihypertensive activity of a new c-Jun N-terminal kinase inhibitor in spontaneously hypertensive rats
_fM. B. Plotnikov, O. I. Aliev, A. Yu. Shamanaev [et al.]
203 _aText
_celectronic
300 _aTitle screen
330 _ac-Jun N-terminal kinases (JNKs) are involved in the myocardial and aortic remodeling, increased arterial tone, and arterial blood pressure elevation associated with hypertension. The aim of the present study was to investigate the antihypertensive effect of a new JNK inhibitor, 1H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt (IQ-1S), on spontaneously hypertensive rats (SHRs). Experiments were performed using normotensive Wistar-Kyoto (WKY) rats and SHRs. Experimental groups of SHRs received IQ-1S intragastrically for 6 weeks in daily doses of 5 and 50?mg/kg; experimental groups of WKY rats received 50?mg/kg IQ-1S according to the same regimen. The IQ-1S administration regimen induced decreases in systolic blood pressure, mean arterial blood pressure, total peripheral resistance, blood viscosity, hematocrit, myocardial cell cross-sectional area, and aortic wall thickness in SHRs vs untreated SHRs. There were no significant differences in systolic blood pressure values between the control and experimental groups of WKY rats during the treatment period. A concentration-dependent decrease in the tone of carotid arterial rings isolated from SHRs was observed after JNK inhibitor application in vitro. Application of the JNK inhibitor diminished endothelin-1 secretion by human umbilical vein endothelial cells in vitro. The main mechanisms of the antihypertensive effect of IQ-1S included the attenuation of blood viscosity due to decreased hematocrit, a vasodilatory effect on arterial smooth muscle cells, and a decrease in endothelin-1 production by endothelial cells.
461 _tHypertension Research
463 _tVol. 43
_v[P. 1068–1078]
_d2020
610 1 _aэлектронный ресурс
610 1 _aтруды учёных ТПУ
610 1 _aJNK inhibitor
610 1 _a1H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt
610 1 _aantihypertensive activity
610 1 _ainhibition of myocardial and aorta remodeling
610 1 _aendothelin-1 production by endothelial cells
610 1 _aингибиторы
610 1 _aнатриевая соль
701 1 _aPlotnikov
_bM. B.
_gMark Borisovich
701 1 _aAliev
_bO. I.
_gOleg Ibragimovich
701 1 _aShamanaev
_bA. Yu.
_gAleksandr Yurjevich
701 1 _aSidekhmenova
_bA. V.
_gAnastasiya Vitaljevna
701 1 _aAnishchenko
_bA. M.
_gAnna Mikhaylovna
701 1 _aFomina
_bT. I.
_gTatjyana Ivanovna
701 1 _aRydchenko
_bV. S.
_gVictoria Sergeevna
701 1 _aKhlebnikov
_bA. I.
_cChemist
_cProfessor of Tomsk Polytechnic University
_f1963-
_gAndrey Ivanovich
_2stltpush
_3(RuTPU)RU\TPU\pers\33927
701 1 _aAnfinogenova
_bYa. J.
_cLinguist
_cLecturer of Tomsk Polytechnic University, Doctor of medical sciences
_f1970-
_gYana Jonovna
_2stltpush
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701 1 _aShchepyotkin
_bI. A.
_cdoctor-biophysicist
_cleading researcher of Tomsk Polytechnic University, candidate of medical science
_f1962-
_gIgor Aleksandrovich
_2stltpush
_3(RuTPU)RU\TPU\pers\37358
701 1 _aAtochin
_bD. N.
_cneuroscientist
_cThe Head of the Laboratory of Tomsk Polytechnic University
_f1960-
_gDmitry Nikolaevich
_2stltpush
_3(RuTPU)RU\TPU\pers\37514
712 0 2 _aНациональный исследовательский Томский политехнический университет
_bИнженерная школа новых производственных технологий
_bНаучно-образовательный центр Н. М. Кижнера
_h7872
_2stltpush
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801 2 _aRU
_b63413507
_c20201103
_gRCR
856 4 _uhttps://doi.org/10.1038/s41440-020-0446-9
942 _cCF