Angiotensin II (Ang II) stimulates the release and gene expression of endothelin-1 in isolated vascular smooth muscle cells. In 47 Sprague-Dawley rats, we assessed the influence of concomitant treatment by the mixed ET(A)/ET(B) endothelin receptor antagonist bosentan (30 mg/kg per day, gavage) on the effect of a 10-day infusion of Ang II (200 ng/kg per minute, SC, osmotic pump) on arterial pres...

Digital ulcers are a well-known problem in patients with systemic sclerosis. Lower extremity ulcers are less prevalent but are also a challenging and underestimated complication of the disease causing important pain and morbidity. Bosentan, an oral dual endothelin receptor antagonist, has been shown to be effective in preventing digital ulcers in patients with systemic sclerosis. A few recent o...

BACKGROUND Bosentan is recommended for symptomatic patients with Eisenmenger syndrome due to simple congenital lesions such as atrial and ventricular septal defects (VSD). However, its long-term efficacy and safety in patients with pulmonary arterial hypertension (PAH) associated with complex congenital heart disease (CHD) is unknown. OBJECTIVES We examined the short- and long-term effects an...

Inhibition of the bile salt export pump (BSEP) has been linked to incidence of drug-induced liver injury (DILI), presumably by the accumulation of toxic bile acids in the liver. We have previously constructed and validated a model of bile acid disposition within DILIsym®, a mechanistic model of DILI. In this paper, we use DILIsym® to simulate the DILI response of the hepatotoxic BSEP inhibitors...

The endothelial actions of insulin remain an area of intense research because they relate to both insulin sensitivity and vascular tone. Physiological doses of insulin evoke endothelium-dependent vasorelaxation in humans; however, this remains a pharmacological phenomenon in rat aortas. Because insulin may stimulate the divergent production of both nitric oxide and endothelin-1, we hypothesized...

OBJECTIVE To describe the pharmacology, pharmacokinetics, efficacy, and safety of bosentan in the treatment of pulmonary arterial hypertension (PAH). DATA SOURCES A MEDLINE and Current Contents search (1966-June 2002) of the English-language literature was conducted to identify published dose-ranging, pharmacokinetic, pivotal efficacy trials and review articles of bosentan and endothelin anta...

The present study describes a simple, accurate, precise, specific and highly sensitive method for the determination of bosentan present in pharmaceutical dosage forms. The method is validated for the determination of bosentan in bulk and tablet dosage form. Bosentan is a dual endothelin receptor antagonist used in the treatment of pulmonary artery hypertension (PAH). The solvent used was methan...

BACKGROUND A variety of stimuli are involved in the pathogenesis of parathyroid gland hyperplasia in renal failure. Recently, it was shown that blocking the signal from the endothelin-1 (ET-1) receptor (ET(A)R/ET(B)R) by a non-selective receptor antagonist, bosentan, reduced parathyroid cell proliferation, parathyroid gland hyperplasia and parathyroid hormone (PTH) levels in normal rats on a ca...

OBJECTIVES Our objective was to evaluate the efficacy and tolerability of bosentan in patients with systemic sclerosis (SSc) who develop ulcers and healed ulcers. We also wanted to analyse the effect of bosentan on other skin and general outcome measurements. METHODS In the present prospective, observational, non-controlled study, we followed all patients with SSc who started treatment with b...

Two endothelin receptor antagonists (ERAs), bosentan and ambrisentan, are currently approved for the treatment of pulmonary arterial hypertension (PAH), a devastating disease involving an activated endothelin system and aberrant contraction and proliferation of pulmonary arterial smooth muscle cells (PASMC). The novel ERA macitentan has recently concluded testing in a Phase III morbidity/mortal...