Pipersentan: A De Novo Synthetic Endothelin Receptor Antagonist that Inhibits Monocrotaline- and Hypoxia-Induced Pulmonary Hypertension

Zhang, Zeyu; Yang, Bai; Li, Xin; Gao, Xiaojian; Li, Chen; Guo, Ge; Chen, Si; Sun, Mingzhuang; Liu, Kang; Li, Yang; He, Kunlun

doi:10.3389/fphar.2022.920222

Cited by 2 publications

(1 citation statement)

References 32 publications

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“…Additionally, hypoxic or monocrotaline-induced rat models exhibited a lung-specific increase in ET-1 peptide, ET-1, and ET A mRNA along with elevated PAP and RV hypertrophy. ET A /ET B receptor antagonists have been shown to prevent and delay plasma ET-1 levels in the 2-week hypoxic prophylactic model only, though they have exhibited results of effectively improved RV hypertrophy and PAP [ 79 , 80 ]. In the systemic circulation, the ET A -selective antagonist BQ123 abolished the pressor effect of ET-1 in rats, while the ET A /ET B antagonist PD145065 suppressed constriction of systemic vessels in response to ET.…”

Section: Mechanism Of the Endothelin Pathway And Its Antagonists In Phmentioning

confidence: 99%

Insights into Endothelin Receptors in Pulmonary Hypertension

Liu

Yuan

Wang

et al. 2023

IJMS

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Pulmonary hypertension (PH) is a disease which affects the cardiopulmonary system; it is defined as a mean pulmonary artery pressure (mPAP) > 20 mmHg as measured by right heart catheterization at rest, and is caused by complex and diverse mechanisms. In response to stimuli such as hypoxia and ischemia, the expression and synthesis of endothelin (ET) increase, leading to the activation of various signaling pathways downstream of it and producing effects such as the induction of abnormal vascular proliferation during the development of the disease. This paper reviews the regulation of endothelin receptors and their pathways in normal physiological processes and disease processes, and describes the mechanistic roles of ET receptor antagonists that are currently approved and used in clinical studies. Current clinical researches on ET are focused on the development of multi-target combinations and novel delivery methods to improve efficacy and patient compliance while reducing side effects. In this review, future research directions and trends of ET targets are described, including monotherapy and precision medicine.

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Section: Mechanism Of the Endothelin Pathway And Its Antagonists In Phmentioning

confidence: 99%

Insights into Endothelin Receptors in Pulmonary Hypertension

Liu

Yuan

Wang

et al. 2023

IJMS

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Investigation of pulmonary artery and circulating endothelin-1 expression in dogs with pulmonary hypertension secondary to myxomatous mitral valve disease

Tangmahakul,

Rungsipipat,

Surachetpong

2024

Vet World

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Background and Aim: Pulmonary hypertension (PH) is a condition characterized by abnormally elevated pressure in the pulmonary vasculature. It is a common complication of myxomatous mitral valve disease (MMVD) in dogs. Several vasoactive substances, including endothelin-1 (ET-1), have been suggested to contribute to pathological changes in the pulmonary arteries of patients with PH. This study aimed to examine the local and systemic expression of ET-1 in dogs with PH secondary to MMVD. Materials and Methods: Lung tissues were collected from 20 client-owned dogs during the first stage of the study and divided into three groups: normal dogs (n = 5), MMVD dogs (n = 8), and MMVD+PH dogs (n = 7). The expression of ET-1 and endothelin A receptor (ETAR) in the pulmonary arteries was determined using immunohistochemistry. Blood samples were collected from 61 client-owned dogs for the second stage of the study and divided into three groups: normal (n = 22), MMVD (n = 20), and MMVD+PH (n = 19). Plasma ET-1 concentration was measured using a sandwich enzyme-linked immunosorbent assay. Results: There was no difference in ET-1 and ETAR expression in the pulmonary arteries among the three groups. Similarly, there was no difference in the plasma ET-1 concentration between the groups. In addition, no correlation was found between the immunohistochemical expression of ET-1 and ETAR and the thickness of the pulmonary arteries or between the plasma ET-1 level and echocardiographic variables. Conclusion: The lack of difference in the expression of ET-1 and ETAR in the pulmonary arteries and in the circulating ET-1 concentration among the studied groups suggests that ET-1 may not be related to the pathological development of PH secondary to MMVD in dogs. Due to the small sample size in this study, further research is needed to confirm these findings. Keywords: canine, degenerative mitral valve disease, endothelin, post-capillary pulmonary hypertension.

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Pipersentan: A De Novo Synthetic Endothelin Receptor Antagonist that Inhibits Monocrotaline- and Hypoxia-Induced Pulmonary Hypertension

Cited by 2 publications

References 32 publications

Insights into Endothelin Receptors in Pulmonary Hypertension

Insights into Endothelin Receptors in Pulmonary Hypertension

Investigation of pulmonary artery and circulating endothelin-1 expression in dogs with pulmonary hypertension secondary to myxomatous mitral valve disease

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