Cell dehydration mediated by Ca2+-activated K+ channels plays an important role in the pathogenesis of sickle cell disease. CD-1 mouse erythrocytes possess a Ca2+-activated K+ channel (Gardos channel) with maximal velocity ( V max) of 0.154 ± 0.02 mmol ⋅ l cells-1 ⋅ min-1and an affinity constant ( K 0.5) for Ca2+ of 286 ± 83 nM in the presence of A-23187. Cells pretreated with 500 nM endothelin...

BACKGROUND Endothelin is a potent endothelium-derived vasoconstrictor peptide with proliferative properties. Elevated levels of the peptide occur in coronary artery disease; however, its pathophysiological role as a regulator of coronary tone and structure is uncertain. Endothelin-receptor antagonists are specific tools to clarify this issue and might be useful in the treatment of coronary arte...

INTRODUCTION Endothelins are involved in tissue inflammation, pain, edema and cell migration. Our genome-wide microarray analysis revealed that endothelin-1 (ET-1) and endothelin-2 (ET-2) showed a marked up-regulation in dorsal root ganglia during the acute phase of arthritis. We therefore examined the effects of endothelin receptor antagonists on the development of arthritis and inflammatory p...

Diabetic kidney disease (DKD) remains the most common cause of chronic kidney disease and multiple therapeutic agents, primarily targeted at the renin-angiotensin system, have been assessed. Their only partial effectiveness in slowing down progression to end-stage renal disease, points out an evident need for additional effective therapies. In the context of diabetes, endothelin-1 (ET-1) has be...

Reactive oxygen species serve as second messengers for signal transduction; however, molecular targets of oxidant signaling have not been defined. Here, we show that ligand-receptor-mediated signaling promotes reactive oxygen species-dependent protein carbonylation. Treatment of pulmonary artery smooth muscle cells with endothelin-1 increased protein carbonyls. Carbonylation of the majority of ...

An increase in coronary perfusion pressure leads to increased cardiac contractility, a phenomenon known as the Gregg effect. Exogenous endothelin (ET)-1 exerts a positive inotropic effect; however, the role of endogenous ET-1 in the contractile response to elevated load is unknown. We characterized here the role of ETA and ETB receptors in regulation of contractility in isolated, perfused mouse...

BACKGROUND/AIM Endothelin-1 plays an important role in the regulation of portal hypertension; endothelin antagonists have been extensively studied in portal hypertensive animals. We aimed to evaluate the efficacy of highly selective endothelin antagonists in partial portal vein ligated (PPVL) rats. METHODS Four groups of 7 male Sprague-Dawley rats were administered orally ABT-627 (ET(A)-selec...

INTRODUCTION Previous studies have suggested that cerebrospinal fluid from patients with subarachnoid hemorrhage (SAH) leads to pronounced vasoconstriction in isolated arteries. We hypothesized that only cerebrospinal fluid from SAH patients with vasospasm would produce an enhanced contractile response to endothelin-1 in rat cerebral arteries, involving both endothelin ETA and ETB receptors. ...