The role of Endothelin-1 in obstructive sleep apnea syndrome and pulmonary arterial hypertension: pathogenesis and Endothelin-1 antagonists.
Obstructive Sleep Apnea Syndrome (OSAS) is a recognized risk factor for cardiovascular disorders and in some cases is complicated with Pulmonary Arterial Hypertension (PAH), as the endothelium is affected. Recent studies provide strong evidence for endothelial dysfunction in obstructive sleep apnea. The resultant vasoconstriction, abnormal cell proliferation and hyper-coagulability may lead to the initiation or progression of atherosclerotic cardiovascular and cerebrovascular disorders, which are frequently encountered in OSA patients. While the currently available therapies for OSAS, such as Continuous Positive Airway Pressure therapy (CPAP therapy), improve endothelial dysfunction, they are not well-tolerated by patients. CPAP therapy can reduce nocturnal hypoxemias and decrease noradrenaline circulating levels, but does not affect ET-1 plasma levels. Potent and selective Endothelin-1 receptor antagonists have been developed and have shown promising results in the treatment of cardiovascular diseases such as pulmonary arterial hypertension, acute and chronic heart failure, hypertension, renal failure, and atherosclerosis. However, results are often contrasting and complicated because of the tissue-specific vasoconstrictor actions of Endothelin-B receptors and the fact that endothelin is an autocrine and paracrine factor whose activity is difficult to measure in vivo.
University of Patras, University Hospital of Patras, Department of Internal Medicine, Division of Pneumonology, Rio, Patras 26500 Greece.
K
K
Karkoulias
D
D
Lykouras
F
F
Sampsonas
P
P
Drakatos
S
S
Canova
G
G
Tsoukalas
K
K
Spiropoulos
D045422:Continuous Positive Airway Pressure; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D017466:Receptors, Endothelin / Q000737:chemistry / Q000378:metabolism; D020181:Sleep Apnea, Obstructive / Q000209:etiology* / Q000378:metabolism / Q000628:therapy
D019332:Endothelin-1; D017466:Receptors, Endothelin