Effects of Bosentan on Peripheral Endothelial Function in Patients with Pulmonary Arterial Hypertension or Chronic Thromboembolic Pulmonary Hypertension

Abstract

Endothelin receptor antagonists (ERAs) have been shown to improve the prognosis of patients with pulmonary arterial hypertension (PAH). However, the effect of the oral dual ERA bosentan on peripheral endothelial dysfunction (PED), as assessed by flow-mediated vasodilation (FMD), in patients with pulmonary hypertension is not well characterized. We investigated the effect of bosentan on PED in patients with PAH or inoperable chronic thromboembolic pulmonary hypertension (CTEPH). A total of 18 patients with PAH and 8 with CTEPH were treated with bosentan. All patients underwent FMD assessment before and after 3 months of bosentan treatment. Whereas FMD increased from 6.01% ± 2.42% at baseline to 8.07% ± 3.18% after 3 months (P < 0.0001) in patients with PAH, those with CTEPH showed no change in FMD after bosentan therapy. In addition, FMD at baseline showed no correlation with pulmonary vascular resistance (r = 0.09) or plasma brain natriuretic peptide levels (r = −0.23) in patients with PAH. Bosentan treatment ameliorated PED in patients with PAH but not in those with inoperable CTEPH. In addition, FMD did not correlate with PAH severity.

Pulmonary microvascular remodeling in chronic thrombo-embolic pulmonary hypertension

“…Endothelin receptor antagonists (ERAs) are an established therapy for PAH (16,32), but conflicting results of ERA therapy have been reported in patients with CTEPH (24,25,44). The 40% higher plasma ET-1 in our porcine model is slightly less than the doubling observed in patient studies.…”

Impaired systemic oxygen extraction in treated exercise pulmonary hypertension: a new engine in an old car?

“… 13 In another study, bosentan increased flow mediated vasodilation in PAH. 14 Our data suggest that if ET-1 blockade increases skeletal muscle blood flow at peak exercise in PAH, it does so indiscriminately, without preferential perfusion of the slow-twitch oxidative muscle fiber. Furthermore, the lowered SVR after treatment with ambrisentan suggests that inappropriate systemic vasodilation secondary to the drug might have adversely affected muscle oxygen uptake and utilization.…”

Endothelial Function in Pulmonary Arterial Hypertension: From Bench to Bedside

“…Following three months of bosentan medication, it was shown that FMD increased in PAH patients but not in CTEPH patients. Nevertheless, FMD did not appear to be correlated with NT-proBNP baseline levels, pulmonary vascular resistance, or the severity of PAH [177].…”