Akademik Veri Yönetim Sistemi
13th International Symposium on Pharmaceutical Sciences, Türkiye, 22 - 25 Haziran 2021
Introduction: Hypertension is one of the most common
cardiovascular diseases and it is also causes structural and functional changes
in the heart (1). Different stressors lead to the accumulation of
unfolded/misfolded proteins, resulting in endoplasmic reticulum (ER)
dysfunction called ER stress (ERS). ERS is recognized as a therapeutic target
for cardiovascular diseases (2). In this study, the effects of ERS inhibitor
4-phenylbutyric acid (4-PBA) on hypertension-induced cardiac dysfunction were examined.
Materials
and Methods: Hypertension
was induced by unilateral nephrectomy followed by deoxycorticosterone
acetate-salt administration in male Wistar rats for 12 weeks. Blood pressure
was measured weekly. ERS inhibitor 4-PBA (150mg/kg/day) was given
intraperitoneally last four weeks. At the end of treatment, right atrium (RA)
and left papillary muscle (LPM) were isolated and rhythmic activity and
contractions of tissues were recorded.
Results: 4-PBA treatment significantly decreased
systolic blood pressure in hypertensive group, but it did not affect body
weight of rats. In Ca2+-free medium, resting tension of RA were
higher in hypertensive rats, this response were significantly lower in 4-PBA
treated-hypertensive group. In Ca2+-free medium,
noradrenalin-stimulated and additional Ca2+-induced contractions and
rhythmic activity of cardiac tissues were similar in all groups. High ryanodine
concentrations-induced contractions of RA (developed tension) were smaller in
4-PBA treated-hypertensive group than hypertensive group. Also, high ryanodine
concentrations-induced contractions of LPM were greater in hypertensive rats
but this response were not changed by 4-PBA treatment.
Conclusions: These findings suggest that ERS
inhibition by 4-PBA improves blood pressure and may have a beneficial effect on
impaired cardiac function in hypertension.