Background: Oral bosentan is an established treatment for pulmonary arterial hypertension (PAH). Objective: To evaluate safety, tolerability, and clinical and haemodynamic effects of bosentan in patients with PAH related to congenital heart disease (CHD). Patients: 22 patients with CHD related PAH (8 men, 14 women, mean (SD) age 38 (10) years) were treated with oral bosentan (62.5 mg62/day for ...

BACKGROUND/AIM Septic shock is an important health problem that vastly alters cardiovascular and hemodynamic status. Increased production of nitric oxide (NO) and endothelin is a counterpart of this endotoxemic state. This study was conducted to test the hypothesis that nonselective NO synthesis blocker (L-NAME), inducible NO synthesis blocker (L-canavanine), or endothelin receptor antagonist (...

BACKGROUND The degree of pulmonary hypertension in healthy subjects exposed to acute hypobaric hypoxia at high altitude was found to be related to increased plasma endothelin (ET)-1. The aim of the present study was to investigate the effects of ET-1 antagonism on pulmonary hypertension, renal water, and sodium balance under acute and prolonged exposure to high-altitude-associated hypoxia. ME...

This study investigated in vivo the putative angiogenic role of endothelin (ET)-1 in a model of ischemia-induced angiogenesis. Ischemia was produced by unilateral femoral artery occlusion in Wistar rats submitted to either chronic ET-1 infusion (2 nmol · kg · min) or to a dual ETA/ETB receptor antagonist (bosentan, 100 mg · kg 21 · d) for 3 and 28 days. Arterial density was evaluated by microan...

Methods and Results-—After systematic searches of the Medline, Embase, and Cochrane Library databases and the ClinicalTrials.gov website, randomized controlled trials with patients receiving ERAs (bosentan, macitentan, or ambrisentan) in at least 1 treatment group were included. All reported adverse events of ERAs were evaluated. Summary relative risks and 95% CIs were calculated using randomor...

Pulmonary arterial hypertension (PAH) is a progressive disease with poor survival outcome. PAH is classified by the 2009 updated clinical classification of pulmonary hypertension and a major subgroup is PAH due to congenital heart disease (CHD) with systemic-to-pulmonary shunt. CHD-PAH is a result of systemic-to-pulmonary shunting and chronic increased flow that ultimately results in adaptation...

I n this issue of the European Respiratory Journal, MATHAI et al. [1] (from Johns Hopkins University, Baltimore, MD, USA) report on their experience with the use of sildenafil, a phosphodiesterase-5 inhibitor, in patients with pulmonary arterial hypertension (PAH) who failed monotherapy with bosentan, an endothelin receptor antagonist. Within a 4-yr period, 82 patients with either idiopathic PA...

To quantitatively understand the events in the human liver, we modeled a hepatic disposition of bosentan and its three known metabolites (Ro 48-5033, Ro 47-8634, and Ro 64-1056) in sandwichcultured human hepatocytes based on the known metabolic pathway. In addition, the hepatotoxicity of Ro 47-8634 and Ro 64-1056 was investigated because bosentan is well known as a hepatotoxic drug. A model ill...

Objective: To evaluate the clinical, exercise, and haemodynamic effects of chronic oral administration of the non-selective endothelin receptor antagonist bosentan on patients with pulmonary arterial hypertension (PAH) related to congenital heart disease (CHD). Design: Prospective non-randomised open clinical study. Setting: Cardiology tertiary referral centre. Patients: 21 patients with a mean...

dssue from sham-operated (Sham), untreated-fistula (Fist), and bosentan (100 mg'kg-1'day-r)-treated animals Gist + Bos) was analyzed for mast cell density, MMP activity, and myocardial collagen volume ' : ' H;h;; ai''i and 5 days after the qeation of an aortocaval fistula. r When compared with untreated flstulas, bosentan treafrnent prevented the marked increase in LV mast cell density at I day...