Pathways and Drugs in Pulmonary Arterial Hypertension – Focus on the Role of Endothelin Receptor Antagonists

Abstract

Pulmonary arterial hypertension (PAH) is a group of diseases characterized by a progressive increase of pulmonary vascular resistance (PVR), initially due to abnormal pulmonary vasoconstriction in response to endothelial injury. Recent studies have here confirmed the prominent role of endothelin (ET)-1 in vasoconstriction and remodelling of the pulmonary microcirculation. In patients who are acute-vasoreactive, classical treatments for PAH are calcium channels blockers (CCBs), while drugs targeting the prostacyclin, nitric oxide and endothelin pathways, i.e., prostanoids, phosphodiesterase (PDE)-5 inhibitors and endothelin receptor antagonists (ERAs), respectively, are indicated in non-vasoreactive patients or in vasoreactive patients not responding to initial CCB therapy. Randomised, placebo-controlled trials have shown that ERAs improve pulmonary haemodynamics, exercise capacity, functional status and clinical outcome in patients with PAH. Here we provide an overview of the currently recommended diagnostic and therapeutic work-up in PAH, with special emphasis on ERAs.

Aldehyde dehydrogenase 2 protects against oxidative stress associated with pulmonary arterial hypertension

“…Many therapeutic drugs continue to be designed and developed for clinical use, but they target a variety of classical signaling pathways, such as prostacyclin, endothelin, and nitric oxide pathways, which are often only effective in a subset of PAH patients [32], [33], [34]. Increasing evidence from both experimental animal models and patients has implicated oxidative stress in PAH pathogenesis [35], [36].…”

Epigenetic regulation of insulin-like growth factor signaling: A novel insight into the pathophysiology of neonatal pulmonary hypertension

“…Through predominantly centered on vasodilation, with many additional emerging therapies directed at cell proliferation and remodeling (reviewed in [22]). The success of those therapies in reducing morbidity and mortality in neonatal PH may occur in a higher percentage if targeted to specific individuals, in the fashion of personalized pharmacotherapy or precisional intervention.…”

“…Such an approach will help in our struggle against this devastating disease, the mortality of which remains high despite the advances of modern drug therapy [22].…”

Heart‑lung crosstalk in pulmonary arterial hypertension following myocardial infarction (Review)

“…ET B1 , ET B2 and ET c have different binding affinities (31). The ET pathway in the pulmonary circulation is composed of ET-1, ET A and ET B (i.e., ET B1 and ET B2 ), with ET-1 exhibiting high-affinity binding (32). ET A and ET B receptors are present in smooth muscle cells and promote vasoconstriction and cell proliferation.…”