JnK inhibitor 11H-indeno [1,2-b]chinoxalin-11-on-oxim sodium salt reduces the development of diastolic dysfunction in spontaneously hypertensive rats

Background. In arterial hypertension (HTN), diastolic dysfunction (DD) of the left ventricle (LV) makes a major contribution to the development of heart failure, so the treatment of DD is an important task. The role of the JNK-dependent pathway in myocardial remodeling in HTN is shown.

Objective. To evaluate the effect of the new JNK inhibitor IQ-1S (11H-indeno [1,2-b]quinoxalin-11-one oxime sodium salt) on parameters of cardiac activity in SHR rats during the period of stable HTN and the formation of DD.

Design and methods. The experiments were carried out on 5 normotensive Wistar-Kyoto (WKY) rats and 10 spontaneously hypertensive rats (SHRs); the experiments included animals that reached the age of 12 weeks. IQ- 1S (50 mg/kg) was administered intragastrically daily to the SHRs of the experimental group (n = 5) for 6 weeks. The WKY control animals (n = 5) and the SHRs (n = 5) received an equivolume amount of distilled water. Systolic blood pressure (SBP) was measured before and after the course of IQ-1S. At the end of the IQ-1S course, body mass (BM) and left ventricular mass (LVM) were evaluated, and contractile myocardial activity (intracardiac sensor) was recorded.

Results. Before and after the IQ-1S course, the values of SBP in the control SHRs were higher than in WKY rats by 30 % and 53 %. After the administration of IQ-1S SHRs showed significantly lower SBP (by 13 %), the LVM/BM index (by 5 %) and the end-diastolic LV pressure (by 40 %) compared to the control SHRs.

Conclusions. Our results confirm the ability of the JNK inhibitor IQ-1S to reduce blood pressure, myocardial hypertrophy and suppress the development of diastolic LV dysfunction in SHRs with the stable HTN.

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