Activation of which of the following causes constriction of pulmonary arteries?: (A) Histamine H2, (B) Muscarinic M3, (C) Endothelin ETA, (D) Adrenergic Alpha-2
Answer is C. Ans. c. (Endothelin ETA) (Ref. H-17th/pg. 233, 1580; Ganong 22nd/pg.602, 666, Ref. Q. 21 of MH-2007)# Endothelin is endothelial cells released potent peptide vasoconstrictor; its concentration is elevated in heart failure and contributes to renal vasoconstriction, Na+ retention, and edema in heart failure. Nitric oxide, which induces vascular relaxation, promotes erection and is opposed by endothelin-1 (ET-1) and Rho kinase, which mediate vascular contraction.# Increased calcium entry into the vascular smooth- muscle cells mediates hypoxic pulmonary vasoconstriction. Pulmonary vascular remodeling in response to chronic hypoxia is also mediated by a reduction in nitric oxide production; an increase in endothelin 1; and increased expression of platelet-derived growth factors, vascular endothelial growth factor, and angiotensin II.# Note: The nonselective endothelin receptor antagonist bosentan is an approved treatment of PAH for patients who are NYHA functional classes III and IV.