Treatment of Secondary Pulmonary Arterial Hypertension With Endothelin Receptor Blockade

Pulmonary Hypertension in End-stage Pulmonary Sarcoidosis: Therapeutic Effect of Sildenafil?

“…Specific treatment options used for sarcoidosis-associated PH include inhaled nitric oxide (iNO), 16 epoprostenol infusion, 17 nebulized iloprost 14 and bosentan. 18,19 Preston et al 16 completed a prospective, observational study of 8 patients with sarcoidosis-related PH with mean MPAP of 55 mm Hg, and 7 of the patients were vasoresponsive to iNO. Of the iNO responders, 5 of 7 commenced treatment with long-term iNO and all improved their 6MWT distance at follow-up; however, only 3 of 5 patients underwent a repeat right-heart catheterization (RHC), and although vasoreactivity to iNO was preserved, baseline MPAP and PVR increased.…”

Comorbidities in interstitial lung diseases

“…In sarcoidosis, sildenafil has improved mean pulmonary arterial pressure and cardiac output in repeat RHC 4 months after treatment [83]. By contrast, bosentan was found to be entirely nonefficacious in fibrotic IIP-PH [57] but may have beneficial effects in some sarcoidosis-PH patients, especially in patients with PH and limited ILD, although the fragmentary nature of current data must be emphasised [84][85][86][87]. Ambrisentan appears to be poorly tolerated in sarcoidosis-PH [88].…”

CPU0123, a novel endothelin receptor antagonist, relieves hypoxic pulmonary hypertension in rats by suppressing excessive ET‐ROS pathway

“…It was not effective on the pulmonary artery, against the systemic arterial system, and likely causes hypotensive responses, which are contraindicated in PAH patients. Data from the present study suggest that nifedipine is less effective in counteracting pulmonary arteriole remodeling, explaining why it is less effective in improving secondary pulmonary hypertension [Sharma et al, 2005].…”

“…Secondary PAH occurs in a variety of systemic collagen vascular diseases, e.g., systemic collagen diseases, pulmonary thromboembolsim, systemic lupus erythromatosus, portopulmonary hypertension, and so on. Despite treatment of the causative disease, progression of secondary PAH continues [Joglekar et al, 2006;Sharma et al, 2005]. The pathological progression of PAH is viewed as an integrated process in which abnormalities of ion channels [Zhang et al, 2004], an excess of ET-1 and cytokines, altered intracellular signaling [Wright et al, 2005], and abnormal 5HT receptor and transporter function [Koehler et al, 2005;MacLean et al, 2000] are likely involved.…”

“…Drug treatment is focused on two modes of action: vasodilators and proliferation reversing agents. The latter is the more favored since PAH is recognized as a vasoproliferative rather than a vasoconstrictive disorder [Sharma et al, 2005].…”