Clinical Pharmacology of Endothelin Receptor Antagonists Used in the Treatment of Pulmonary Arterial Hypertension
Résumé
Pulmonary arterial hypertension (PAH) is a devastating life-threatening disorder characterized by elevated pulmonary vascular resistance leading to elevated pulmonary arterial pressures, right ventricular failure and ultimately death. Vascular endothelial cells mainly produce and secrete endothelin (ET-1) in vessels that lead to a potent and long-lasting vasoconstrictive effect in pulmonary arterial smooth muscle cells. Along with its strong vasoconstrictive action, ET-1 can promote smooth muscle cell proliferation. Thus, ET-1 blockers have attracted attention as an antihypertensive drug and the ET-1 signaling system has paved a new therapeutic avenue for the treatment of PAH. The present chapter outlines not only the current understanding of the pathogenic role played by ET-1 signaling systems in the pathogenesis of PH, but also on the clinical pharmacology of endothelin receptor antagonists (ERA) used in the treatment of PAH.
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