Endothelium-derived NO is released in response to which stimuli?

• A. Shear stress and acetylcholine
• B. Low oxygen
• C. Norepinephrine
• D. Vasoconstriction only

Answer: (A)

Endothelium-derived NO is released when the endothelium detects signals that raise intracellular calcium and activate endothelial nitric oxide synthase (eNOS). The primary triggers are increased shear stress from blood flow, a mechanical cue that stimulates endothelial cells, and acetylcholine, which binds muscarinic receptors on the endothelium and also raises intracellular Ca2+. In both cases, Ca2+-activated eNOS converts L-arginine to NO. The NO then diffuses into the adjacent smooth muscle, activates soluble guanylate cyclase, increases cGMP, and causes relaxation and vasodilation. This mechanism underlies flow-mediated dilation and the response to acetylcholine. The other options don’t directly provoke the endothelium to release NO: low oxygen isn’t a primary NO trigger in most vessels, norepinephrine mainly promotes vasoconstriction via smooth muscle receptors, and vasoconstriction alone doesn’t drive NO release.