Which of the following is a true statement about Endothelin-1, a potent vasoconstrictor?
(B) Produced in increased amounts in Pulmonary Arterial HypertensionoEndothelin 1 (ET-1), (preproendothelin-1) (PPET1), is a potent vasoconstrictor that in humans is encoded by the EDN1 gene and produced by vascular endothelial cells.oThe protein encoded by this gene is proteolytically processed to release a secreted peptide termed endothelin 1.oEndothelin 1 is one of three isoforms of human endothelin.oPreproendothelin is precursor of the peptide ET-1.oEndothelial cells convert preproendothelin to proendothelin and subsequently to mature endothelin, which the cells release[?]ENDOTHELIN is a potent peptide vasoconstrictor released by endothelial cells.oIts concentration is elevated in heart failure and contributes to renal vasoconstriction.oBosentan is an endothelin antagonist used to treat pulmonary arterial hypertension.[?]Endothelin-1 (ET-1) is a potent pulmonary vasoconstrictor that is produced in increased amounts in Pulmonary Arterial Hypertension (PAH).oET-1 contracts vascular smooth muscle cells and causes proliferation mainly via ETA receptors.oETB receptors mediate the release of prostacyclin and NO from endothelial cells.oSeveral endothelin antagonists are available for the treatment of PPAH.oBosentan (TRACLEER) was the first ET antagonist developed and is a antagonist of both ETA and ETB receptors.oSeveral longterm clinical trials have now established the efficacy of oral bosentan in reducing symptoms and improving mortality in PPAH.oStarting dose is 62.5 mg twice daily for 4 weeks, then increasing to the maintenance dose of 125 mg twice daily.oThe drug is generally well tolerated.oAdverse effects include-Abnormal liver function tests-Anemia-Headaches-Peripheral edema-Nasal congestion.oGiven the risk of serious liver injury, liver aminotransferases should be monitored monthly.oA class effect is a risk of testicular atrophy and infertility; bosentan is potentially teratogenic.oEndothelin Antagonists.oEndothelin has been implicated in some of the structural changes that occur in asthma and COPD.oEndothelin antagonists are approved for the treatment of pulmonary hypertension and might be useful in treating the structural changes that occur in asthma and COPD,
Used in Hypertension treatment
Produced in increased amounts in Pulmonary Arterial Hypertension
Dilates vascular smooth muscle cells
Safely indicated in liver injury
C.V.S