THE EFFECT OF 4-PHENYLBUTYRIC ACID ON HYPERTENSION-INDUCED CARDIAC IMPAIRMENTS


Bal N. B. , Han S. , Uludağ M. O. , Demirel Yılmaz E.

13th International Symposium on Pharmaceutical Sciences (ISOPS) , Ankara, Turkey, 22 - 25 June 2021, pp.75

  • Publication Type: Conference Paper / Summary Text
  • City: Ankara
  • Country: Turkey
  • Page Numbers: pp.75

Abstract

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.