Endothelin-1 (ET-1), secreted by vascular endothelial cells, is the most potent endogenous vasoconstrictor. ET-1 acts through two receptors: ETA on vascular smooth muscle and ETB on endothelial cells. The ETB receptor mediates which opposing action?

• A ETB on smooth muscle causes direct vasoconstriction synergistic with ETA receptor activation
• B ETB on endothelial cells stimulates nitric oxide (eNOS) and prostacyclin release, causing vasodilation and counterbalancing ETA-mediated vasoconstriction ✓
• C ETB on endothelial cells promotes ET-1 secretion as a positive feedback mechanism
• D ETB on endothelial cells activates ROCK (Rho kinase) to cause vascular remodeling

Explanation

ETA receptors are located on vascular smooth muscle and mediate vasoconstriction via Gq → PLC → IP3-mediated Ca²⁺ release and PKC activation. ETB receptors are located on endothelial cells and on some smooth muscle cells. ETB on endothelium signals via Gi/eNOS to produce nitric oxide and also stimulates prostacyclin (PGI2) release, both of which cause smooth muscle relaxation — counterbalancing the ETA-mediated constriction. ETB also mediates clearance of circulating ET-1. Non-selective endothelin antagonists (bosentan) block both receptors; selective ETA blockers (ambrisentan) preserve the ETB vasodilatory pathway, which may offer theoretical benefits in pulmonary arterial hypertension.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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