A researcher infuses a vasoactive substance into an isolated arterial segment and observes contraction that persists even after the substance is washed out. She then endothelium-denudes the same segment and repeats the experiment; the vasoconstriction now promptly reverses on washout. Which of the following BEST explains this observation?

• A The substance activates endothelin-1 gene transcription in endothelial cells; autocrine endothelin-1 then sustains smooth muscle contraction through ETA receptors even after the original stimulus is removed ✓
• B The substance causes persistent elevation of smooth muscle intracellular Ca²⁺ through activation of non-inactivating L-type channels, independent of endothelium
• C Without endothelium, the substance cannot bind because its receptor is exclusively endothelial
• D The substance depletes endothelial nitric oxide synthase, removing the nitric oxide that normally opposes contraction; denudation removes this potential and contraction cannot persist

Explanation

Endothelin-1 (ET-1) is a potent vasoconstrictor synthesized and released primarily by vascular endothelial cells. Its production is triggered by mechanical stress, hypoxia, thrombin, and various vasoactive substances. Once secreted, ET-1 acts on ETA receptors on vascular smooth muscle causing prolonged contraction; it also acts on ETB receptors on endothelial cells triggering NO and prostacyclin release (creating some auto-regulation). The persistence of contraction even after removal of the stimulus, and its dependence on the endothelium, is characteristic of ET-1-mediated signaling. Denudation removes the endothelial cells, eliminating ET-1 production, so the contraction promptly reverses when the original stimulus is washed out. Options B and D are mechanistically incorrect. Option C is wrong because smooth muscle does have receptors for many vasoactive substances.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.