Abstract
Pulmonary arterial hypertension is a fatal disease, especially when it causes right heart failure (RHF). However, it is difficult to treat. It has been reported that trapidil (Tra) can improve the redox balance and cardiac conditions. In this study, we investigated the effect of Tra on RHF induced by monocrotaline (MCT) in rats. Male Wistar rats were treated with MCT or Tra. Treatment lasted 28 days, then rats were euthanized after echocardiography and catheterization. Subsequently, lungs and right ventricular myocardia were evaluated by hematoxylin and eosin, Masson, and TUNEL staining. Protein expression was detected by western blotting. We found remarkably expanded right ventricle end-diastolic volume, decreased partial pressure of oxygen (PaO2), increased partial pressure of carbon dioxide (PaCO2), right ventricular systolic pressure, mean pulmonary arterial pressure, lung/body weight, and liver/body weight in the RHF rat group, as well as increases in the apoptosis rate and the expression of endoplasmic reticulum stress (ERS)-related proteins. However, these changes were significantly inhibited by Tra. Our data suggested that inhibition of ERS is essential for improving RHF, and that therapeutic intervention of Tra in RHF rats works by reducing ERS.
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Abbreviations
- HF:
-
Heart failure
- RHF:
-
Right heart failure
- Tra:
-
Trapidil
- TXA2:
-
Thromboxane A2
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Acknowledgements
We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript. This work was supported by the National Natural Science Foundation of China (Grant No. 81360587, 81460761, 81760780), the Natural Science Foundation of Inner Mongolia (Grant No. 2016BS0806, 2016MS08126, 2019ms08031), and Youth Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region (Grant No. NJYT-19-B14), Open subject of Inner Mongolia Provincial Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System (Grant No. MDK2018074).
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Wang, Y., Wang, Y., Wei, C. et al. Trapidil determines the fate of RHF rats through inhibition of ER stress. Arch. Pharm. Res. 43, 409–420 (2020). https://doi.org/10.1007/s12272-020-01222-5
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DOI: https://doi.org/10.1007/s12272-020-01222-5